RARE DISEASE
Nocardiosis
Nocardiosis
Nocardiosis
Drug discovery
0
drugs
With orphan designations
Overview
Nocardiosis is a bacterial infection caused by Nocardia species, aerobic soil-dwelling gram-positive bacilli. It primarily presents as pulmonary, cutaneous, or disseminated disease, with frequent CNS involvement. Diagnosis relies on culture and molecular methods, often requiring prolonged incubation. Mortality rates range from 10% (localized) to 80% (CNS), influenced by immune status and treatment delays [1][4][10].
Therapies
First-line: Trimethoprim-sulfamethoxazole (TMP-SMX) or combination therapy (e.g., imipenem + amikacin) for severe/disseminated cases [1][3][14].
Treatment duration: 6–12 months, adjusted based on susceptibility testing and clinical response [3][10].
Surgical drainage of abscesses and early CNS imaging are adjunctive [1][8].
Categories: rare infectious diseases
Research Papers
1,086 drug discovery papers about Nocardiosis. Recent publications:
1,086 drug discovery papers about Nocardiosis. Recent publications:
categories:
Small molecules
small molecules
2026-08-16 | Disseminated Nocardia pseudobrasiliensis infection in a case of juvenile systemic lupus erythematosus on immunosuppressive therapy.
Nocardiosis is an uncommon infection that presents as a chronic, debilitating illness with radiographic manifestations simulating lung cancer or tuberculosis. Immunocompromised hosts may develop a fulminant disease resembling acute bacterial pneumonia or disseminated disease. We report a case of a juvenile lupus who developed disseminated Nocardia pseudobrasilienisis infection in form of necrotizing pneumonia, subcutaneous nodules and central nervous system (CNS) lesion in the right parietal lobe, following inadvertent hiking of steroids after a minor organ flare. This case was successfully treated with intravenous meropenem, amikacin, and oral cotrimoxazole therapy for 6 weeks which lead to resolution of pneumonia, and partial resolution of of the cutaneous and CNS lesion. As the patient was immunosuppressed, and had disseminated nocardiosis, we planned to put her on oral cotrimoxazole for the next 1 year.
2026-07-31 | Disseminated Nocardia farcinica with multiple cerebral abscesses in a patient receiving induction immunosuppression for autoimmune hepatitis: case report.
Nocardiosis is an opportunistic infection caused by aerobic, Gram-positive actinomycetes of the genus Nocardia that most often affects patients with impaired cell-mediated immunity, including those receiving corticosteroids or other immunosuppressive therapies. Disseminated disease frequently involves the central nervous system, where a systematic review reported an overall case fatality rate of 22.8%, and Nocardia farcinica is the most commonly identified species. We report a case of disseminated Nocardia farcinica with multiple cerebral abscesses in a patient receiving induction immunosuppressive therapy for autoimmune hepatitis. A 55-year-old man with a history of autoimmune hepatitis and occupational soil exposure presented with 4-5 week history of progressive cognitive impairment, dysarthria, and right upper extremity weakness. Two months earlier, he had been treated with high-dose corticosteroids and azathioprine and prescribed trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, which had been interrupted for an estimated 2-4 weeks before presentation during ongoing corticosteroid therapy. Upon admission, laboratory tests demonstrated neutrophil-predominant leukocytosis with lymphopenia, and liver function tests showed substantial improvement compared to his initial presentation of autoimmune hepatitis. Neuroimaging revealed multiple ring-enhancing intracerebral lesions with surrounding vasogenic edema. Stereotactic aspiration of a cerebral abscess and drainage of a concurrent retroperitoneal collection grew Nocardia farcinica, confirming disseminated nocardiosis. Antimicrobial therapy was transitioned to imipenem-cilastatin and TMP-SMX based on susceptibility testing. During infection management, azathioprine was paused, and prednisone was continued at a dose of 25 mg/day, followed by a biochemical autoimmune hepatitis flare requiring hepatology-guided monitoring. The patient demonstrated gradual neurologic improvement and was discharged to inpatient rehabilitation after an 18-day hospitalization. Disseminated nocardiosis should be considered for immunosuppressed patients with autoimmune hepatitis presenting with subacute neurological decline and ring-enhancing brain lesions, particularly during outpatient immunosuppression transitions when antimicrobial prophylaxis may be interrupted or incompletely reconciled. The patient demonstrated progressive neurological improvement and radiographic abscess reduction after 3 months of susceptibility-guided combination therapy, reinforcing the importance of early tissue diagnosis and neurosurgical intervention in this population.
2026-07-18 | Structure-based virtual screening identifies dicoumarol as a potent InhA inhibitor against Nocardia seriolae infection in largemouth bass (Micropterus salmoides)
Nocardiosis, caused by Nocardia seriolae , represents a critical bottleneck in the intensive aquaculture of largemouth bass ( Micropterus salmoides ), complicated by the pathogen's unique mycolic acid barrier and emerging multidrug resistance. To overcome the inefficiencies of traditional random screening, this study adopted a structure-based drug discovery strategy targeting InhA, the enoyl-acyl carrier protein reductase of the type II fatty acid synthase (FAS-II) pathway. Using AlphaFold 3-based structural modeling and high-throughput virtual screening, we identified dicoumarol (DIC) as a lead candidate. Biophysical assays, including isothermal titration calorimetry and fluorescence quenching, demonstrated high-affinity binding of DIC to the hydrophobic substrate-binding pocket of N. seriolae InhA (nsInhA). In vitro , DIC showed potent bactericidal activity and reduced intracellular bacterial loads in EPC cells. In vivo , dietary administration of DIC significantly improved survival and ameliorated granulomatous pathology in infected fish. Transcriptional analysis further showed reduced expression of the pro-inflammatory cytokines il1b and il6 in treated fish, consistent with an attenuated inflammatory burden during infection. Together, these findings support nsInhA as a druggable target and identify DIC as a promising therapeutic lead for the control of fish nocardiosis.
2026-07-16 | Disseminated nocardiosis in a Japanese raccoon dog (Nyctereutes procyonoides viverrinus).
A captive male Japanese raccoon dog died after self-mutilation by biting its tail and developing anorexia. At necropsy, ulceration of the tail root and pelvic region, an abdominal mass, multifocal nodules in the lungs, and thrombi in the heart were observed. Histopathological examinations revealed multifocal pyogranulomatous inflammation in the lungs, abdominal mass, spleen, brain, liver, and kidneys. Gram-positive bacterial aggregates were observed in the lungs, abdominal mass, and spleen. These organisms were partially acid-fast and periodic acid-Schiff-positive, and branching filaments were observed on Grocott's methenamine silver staining. Nocardia aobensis was identified in the abdominal mass by PCR and sequence analysis. These findings suggest that N. aobensis should be considered a potential cause of disseminated pyogranulomatous disease in animals.
2026-07-08 | Oral amoxicillin-clavulanate: an alternative treatment to refractory Nocardia keratitis-a case report.
Bacterial keratitis (bacterial corneal infection) is a serious, vision-threatening disease caused by a wide range of bacterial species. The gram-positive bacterium Nocardia spp. is increasingly recognized in keratitis, yet is particularly challenging to treat due to delayed diagnosis and limited efficacy of current ophthalmic therapeutics. Antimicrobial resistance among clinical Nocardia isolates is also rising, further complicating patient outcomes. Herein, we report a case of Nocardia amikacinitolerans keratitis, resistant to amikacin, ciprofloxacin, moxifloxacin, clarithromycin, and ceftriaxone, resulting in a complicated therapeutic course. A 53-year-old female presented with bacterial keratitis of the right eye, which over the course of 32 months progressed to scleritis (infection of the sclera) and a progressive, significant decrease in visual acuity to hand motion despite exhaustive topical and systemic antimicrobial therapies. While there is a general lack of efficacy of systemic therapies for bacterial keratitis, oral amoxicillin-clavulanate ultimately proved successful in resolving the infection. As Nocardia spp. ocular infections become more prevalent, this report underscores the highly virulent nature of this pathogen and provides insights into potential therapeutic modalities in the setting of multidrug resistance.
vaccines
2026-01-12 | Protective efficacy of the optimized GluB-MTAP fusion subunit vaccine against Nocardia seriolae infection in largemouth bass (Micropterus salmoides).
Nocardia seriolae is the predominant causative agent of piscine nocardiosis, exhibiting broad piscine host specificity along with prolonged latency periods and high mortality rates, thereby posing a severe threat to global fish health. However, reliably effective control measures remain limited. Subunit vaccines, derived from virulence factors or immunodominant proteins of the pathogen, are widely acknowledged as one of the most secure and potent strategies for mitigating disease outbreaks. Here we focused on five T7SS gene cluster proteins (MTAP, HP05, HP23, HP24, and VST) and the dominant N. seriolae secretory protein (GluB) as subunit vaccine candidates through whole-genome sequencing and HPLC-MS analysis, identifying GluB and MTAP as superior antigens through efficacy-based screening assessing immunogenicity, serum antibody titers, and protective efficacy. To further enhance the protective efficacy, we engineered a novel fusion antigen composed of GluB and MTAP. In Micropterus salmoides, immunization with the GluB-MTAP fusion antigen elicited robust defensive responses at 28 days post-immunization, characterized by enhanced antioxidant capacity and amplified inflammatory and humoral immunity. The fusion vaccine conferred significant protection against N. seriolae challenge with a relative percentage survival (RPS21d) of 70 %, achieving 72.3 % absolute survival compared to 8 % in controls, which represented absolute survival improvements of 6.3 % over GluB-monovalent (66 %) and 18.3 % over MTAP-monovalent immunization (54 %). Collectively, the GluB-MTAP subunit vaccine demonstrates substantial efficacy against nocardiosis in M. salmoides, providing a mechanistic platform for investigating Nocardia-host interplay. This study further establishes a rational framework for anti-Nocardia seriolae vaccine development and advances sustainable aquaculture disease control strategies.
2025-12-13 | Develop subunit vaccines against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂) using two resuscitation-promoting factors.
Fish nocardiosis is a bacterial disease epidemic in aquaculture, and Nocardia seriolae is its main pathogen. The prevention and treatment of N. seriolae infection face multiple challenges, such as the unclear mechanism of chronic infection, resistance to phagocyte killing, and unsatisfied therapeutic efficacy of antibiotics. Resuscitation-promoting factors (Rpfs) are widely found in gram-positive bacteria, and have been reported to be vaccine candidates against tuberculosis and nocardiosis. In this study, RpfB and RpfD of N. seriolae ZJ0503 were obtained by prokaryotic expression and combined with Freund's Incomplete Adjuvant (FIA) as subunit vaccines, respectively. Finally, their efficacy were accessed in hybrid snakehead. The results showed that the relative survival rates (RPS) of subunit vaccines RpfB + FIA and RpfD + FIA were 77.78 % and 70.37 %, respectively. Histopathological examination revealed that hybrid snakehead did not show cytotoxic activity after intraperitoneal injection of RpfB + FIA and RpfD + FIA vaccines. In addition, both RpfB + FIA and RpfD + FIA vaccines increased the activity of multiple nonspecific immune parameters such as LYZ, CAT, ACP, AKP and SOD in the fish serum. The production of specific antibodies (IgM) and the expression of immune-related genes (tnfα, il-1β, cd4, cd8α, mhciα and mhciiα) were significantly increased compared with the control groups. In summary, RpfB and RpfD subunit vaccines were safe and can effectively protect hybrid snakehead from N. seriolae infection, and are ideal vaccine candidates for preventing fish nocardiosis.
2025-11-17 | An isocitrate lyase gene-deleted strain of Nocardia seriolae in live attenuated vaccine development against fish nocardiosis.
Fish nocardiosis caused by Nocardia seriolae is a severe bacterial disease in aquaculture, causing significant economic losses. The effectiveness of antibiotics in dealing with nocardiosis induced by N. seriolae is not satisfactory. NsICL is a potential virulence factor in N. seriolae based on its crucial role in the glyoxylate cycle, its identity as a secreted protein, and its established role in virulence and intracellular survival in homologous pathogens such as Mycobacterium tuberculosis. so, the NS-ΔICL deletion strain was constructed to investigate its function. The NsICL gene was knocked out via homologous recombination to generate the mutant strain NS-ΔICL. Comparative analysis of morphology, growth, and virulence was performed between the mutant and wild-type strains. The NS-ΔICL strain was used to immunize hybrid snakehead (Channa maculata♀ × Channa argus♂), with immune responses evaluated through non-specific immune parameters, specific antibodies, and expression levels of immune-related genes. Protective efficacy was assessed by challenge tests. NS-ΔICL showed reduced virulence (LD50 = 2.60 × 105 cfu/fish) compared to the wild-type strain (LD50 = 4.32 × 104 cfu/fish). Immunized fish exhibited significantly higher levels of non-specific immune factors (AKP, ACP, POD, LZM) and specific IgM antibodies. Immune-related genes (MHCIα, CD4, IL-8) were upregulated in vaccinated fish. Relative percentage survival (RPS) was 77.03% in vaccinated fish after challenge tests, which indicating strong protective efficacy. The NS-ΔICL deletion strain was successfully constructed in this study. It can not only induce humoral and cellular immunity in fish but also effectively protect fish against N. seriolae infection. These results provide a foundation for the development of a live attenuated vaccine for treating fish nocardiosis.
2025-07-03 | Surface display of Nocardia seriolae HRP1 on Bacillus subtilis and its application as live vaccine for largemouth bass.
Micropterus salmoides, adaptable and fast-growing, is a major farmed fish in China. Intensive farming causes multiple diseases, especially hard-to-treat nocardiosis. Vaccines are an effective and safe prevention and control strategy against fish diseases. In this experiment, the highly antigenic HRP1 gene of Nocardia seriolae (N. seriolae) was displayed on the surface of Bacillus subtilis (B. subtilis), and an oral vaccine (HRP1-cotC-B. subtilis) was successfully developed. Immune responses in inoculated fish were tested intermittently over 5 weeks post-administration. Immune protection was evaluated via challenge test. Serological parameters testing showed that the activity of lysozyme and Glutathione Peroxidase (GSH-Px) were significantly increased at the 7th and 21st day post-immunization, and the activity of Alkaline Phosphatase was extremely increased compared to the control. qRT-PCR detection found that oral vaccine could significantly boost the IgM expression of spleen and head-kidney. The expression of spleen major histocompatibility complex (MHC) was enhanced, MHCII at the 7th, 21st day and MHCI at 35th day post-immunization respectively. MHCI has an increasing trend in the head-kidney. CD8 increased in both spleen and head-kidney at different stages of immunization. The inflammatory cytokine il-1β and anti-inflammatory cytokine TGF-β significantly increased in head-kidney at 35th day after immunization. The live bacterial vaccine altered the composition of the intestinal flora, demonstrated a decline in Firmicutes and an increase in Fusobacteria, and a significant decrease in Clostridium replaced by Cetobacterium at the genus level. Largemouth bass immunized with HRP1-cotC-B. subtilis spores exhibited a 18.18% relative survival rate after N. seriolae infection. In conclusion, this study developed a novel oral vaccine against N. seriolae in largemouth bass using B. subtilis spore surface display technology. Oral vaccination improves nonspecific immunity, induces innate and cellular immunity, strengthens bacterial resistance, and increases survival after pathogen infection. This offers an effective strategy for controlling fish nocardiosis in aquaculture.
2025-07-01 | Immunoinformatics-Guided Whole Proteome-Based Multi-Epitope mRNA Vaccine Design Against Nocardia asteroides Using Surface Antigens-A Subtractive Proteomics and Reverse Vaccinology Approach.
Nocardiosis is caused by the aerobic gram-positive bacterium Nocardia asteroides which is multidrug-resistant and primarily affects immunocompromised individuals. This study aims to design a broad-spectrum vaccine against Nocardiosis. We used subtractive proteomics and vaccinomics approaches to identify vaccine candidates to design an epitope-based vaccine against Nocardiosis. Four proteins in the outer membrane and extracellular regions were shortlisted on the basis of immunogenic parameters. T- and B-cell epitopes were predicted on the basis of IC50 < 200 nM, and a multi-epitope vaccine construct was designed using six overlapping CTL, HTL, and B-cell epitopes conjugated by appropriate linkers. A highly immunogenic adjuvant was integrated at the N-terminus of the multi-epitope vaccine to stimulate a robust immune response. The tertiary structure of the vaccine construct was predicted and validated with the 96% residues in the favorite region of the Ramachandran plot and a Z-score of -4.76. The proposed vaccine exhibited strong immunological and physicochemical features. High docking scores and strong binding energies of approximately -1051.9 to -1274.5 kcal/mol with human immune receptors ensured that the designed vaccine construct could induce potential immunogenic responses in the host immune system. The efficacy of the vaccine was evaluated by the immune simulation to determine the potential of the vaccine to simulate innate and adaptive immunity with the development of long-lasting memory immune cells. The molecular dynamic simulation of a 100 ns study was conducted to determine the structural stability and molecular function of the designed vaccine in the cellular microenvironment. In silico restriction cloning analysis determined the successful expression of the engineered vaccine construct in Escherichia coli plasmid with a size of 6323 bp. On the basis of the current study, we assume that the proposed vaccine is worthy of further in vitro in vivo and in vivo validations to ensure the efficacy of the engineered vaccine in this study.
proteins
2026-07-18 | Genetic and functional evidence links tgfbr2 to Nocardia seriolae resistance in spotted sea bass.
Spotted sea bass (Lateolabrax maculatus) is an economically important aquaculture species in China, but nocardiosis caused by Nocardia seriolae results in high mortality and economic losses. To investigate the genetic basis of disease resistance, two experimental populations are challenged and analyzed by genome-wide association studies (GWAS). We identify 112 SNPs, including 17 nonsynonymous variants in tgfbr2. Functional enrichment analysis highlights the TGF-β signaling and its related pathways. Structural analysis reveals that TGFBR2 is highly conserved, and mutations in the intracellular kinase domain may alter receptor conformation. Recombinant TGF-β1a modulated splenic lymphocytes transcription, upregulating foxp3b, il10 and smad7, while suppressing proinflammatory cytokines. The tgfbr2 mutation impaires downstream SMAD phosphorylation and reduces transcriptional activation of the foxp3b promoter. These results identify key genetic loci for resistance to N. seriolae and establish a mechanistic connection between TGF-β signaling and immune regulation, providing a foundation for molecular breeding of disease-resistant spotted sea bass.
2026-06-26 | Genome-wide identification of the cystatin gene family and functional characterization of cystatin B in flathead mullet (Mugil cephalus).
The cystatin superfamily is a class of endogenous cysteine protease inhibitors that play a key role in immune regulation and host defense. However, there remains a lack of genome-wide identification and functional studies of this gene family in the flathead mullet. Therefore, this study conducted a systematic identification of the cystatin gene family in flathead mullet at the genome-wide level and further characterized the function of McCysB (Mugil cephalus Cystatin B). The results revealed that seven cystatin genes were identified in the flathead mullet genome, which were classified into three subfamilies, namely stefins (type I), cystatins (type II), and kininogens (type III), based on phylogenetic analysis. based on phylogenetic analysis. Structural and conserved motif analysis indicated that all members contained a highly conserved cystatin domain, suggesting functional conservation during evolution. Chromosomal mapping revealed that these genes were unevenly distributed across four chromosomes and exhibited tandem duplication events. Collinearity analysis further revealed the evolutionary conservation of the cystatin gene locus in teleosts. Tissue expression profiling indicated that most McCys genes were highly expressed in immune-related tissues, with the most significant expression levels observed in the kidneys. Following infection with Vibrio harveyi, the expression level of McCysB was significantly upregulated, suggesting its potential involvement in the antimicrobial immune response. Furthermore, this study successfully expressed and purified the recombinant McCysB (rMcCysB), and the in vitro functional assays confirmed that this protein exhibited dose-dependent antibacterial activity against Staphylococcus aureus, Nocardia seriolae, Escherichia coli and V. harveyi, with a more pronounced inhibitory effect against Gram-negative bacteria. In summary, this study systematically elucidated the molecular characteristics, evolutionary patterns, and potential immunological roles of the cystatin gene family in the flathead mullet and revealed McCysB as a potential immune effector molecule, providing a candidate target for the development of antimicrobial strategies in aquaculture.
2026-03-13 | An Unusual Case of Cutaneous Nocardia cyriacigeorgica Infection Assuming the Appearance of Shingles.
Nocardia is an opportunistic organism that commonly infects the lungs of the immunocompromised and can cause disseminated infections. Diagnosis of Nocardia cyriacigeorgica is through culture and susceptibilities, aided by 16S rRNA sequencing. We report a case of a shingles-like rash eruption due to Nocardia cyriacigeorgica in a 69-year-old patient with a history of bilateral lung transplant.
2026-02-10 | Nocardiosis in Immunocompromised Hosts: A Retrospective, Single-Center Analysis of Clinical and Microbiological Determinants of Central Nervous System Involvement.
Immunocompromised patients are at risk of disseminated nocardiosis, which can involve the central nervous system. The factors mediating dissemination to the central nervous system in this patient population have not been fully characterized. This study aimed to identify patient and pathogen-related variables associated with a higher risk of central nervous system infection among immunocompromised patients with nocardiosis. Retrospective single-center analysis of all immunocompromised patients diagnosed with nocardiosis between 2013 and 2024. Patients without brain imaging were excluded from the analysis. A case-control analysis was conducted to compare patients with central nervous system involvement (cases) and those without (controls), examining demographic, immunosuppression-related, and pathogen-related variables through univariate analysis. A total of 54 patients were included in the study. The most common type of immunosuppression was solid organ transplantation (39%). The prevalence of central nervous system involvement was 30%. In univariate analysis, white, non-Hispanic patients and patients with bronchiectasis had lower odds of central nervous system involvement. In contrast, patients infected with Nocardia farcinica had higher odds of central nervous system involvement. Immunocompromised patients with nocardiosis who had brain involvement did not differ significantly from those without brain involvement in terms of immunosuppression-related factors. Instead, this difference appears to be explained by differences in the virulence of Nocardia species, particularly N. farcinica.
2026-01-30 | Disseminated Nocardia ignorata Infection with Splenic and Brain Involvement in Patient with Large B-Cell Lymphoma.
A 79-year-old man in the United States with large B-cell lymphoma and chronic obstructive pulmonary disease had disseminated Nocardia ignorata infection involving the brain and spleen. Despite antimicrobial therapy, he died from complications. This rare manifestation highlights the need to consider Nocardia in immunocompromised patients with central nervous system and abdominal lesions.
antibodies
2025-01-11 | Spontaneous remission of Pneumocystis jirovecii pneumonia followed by severe pulmonary nocardiosis in a patient with HIV infection: A case report.
We describe a rare case of spontaneous remission of Pneumocystis jirovecii pneumonia (PCP) in a 42-year-old patient with human immunodeficiency virus (HIV) infection, followed by severe pulmonary nocardiosis. To our knowledge, this is the first report of spontaneous remission of PCP in a completely untreated patient with HIV infection. The patient, a bisexual Japanese man, presented with fever and anorexia and had a history of non-compliance with antiretroviral therapy (ART) for 13 years. PCP was initially suspected on the basis of imaging and laboratory findings, but the patient refused further evaluation and treatment. Surprisingly, the evidence of PCP infection disappeared without intervention. Four months later, the patient was diagnosed with severe pulmonary nocardiosis caused by Nocardia beijingensis, which was confirmed by bronchoscopy and culture. Antibiotic therapy and ART resulted in significant clinical improvement. Based on this case, we propose that N. beijingensis infection may contribute to spontaneous remission of PCP, possibly through production of antimicrobial substances and induction of granulocyte-macrophage colony-stimulating factor. On the other hand, fluctuations in immune function, particularly variability in CD4+ T lymphocytes, may also contribute. This report highlights the complex interplay between opportunistic infections in immunocompromised patients. These findings may provide valuable insights into the management of PCP.
2024-08-02 | TREATMENT OF NOCARDIA CHORIORETINITIS-RELATED CHOROIDAL NEOVASCULARIZATION WITH AFLIBERCEPT: A CASE OF UNVEILED IMMUNOCOMPROMISE WITH ANTI-GM-CSF ANTIBODIES.
The purpose of this study was to describe a case of Nocardia chorioretinitis-related choroidal neovascularization in a patient with anti-GM-CSF antibodies with resolution of choroidal neovascularization and visual recovery after a series of intravitreal anti-vascular endothelial growth factor. This study is a case report. In this case, a 50-year-old woman, thought to be immunocompetent, presented with metamorphopsia and decreased visual acuity in the left eye in the setting of disseminated nocardiosis . She had evidence of a subfoveal Nocardia lesion with subretinal fluid and choroidal neovascularization. After a series of off-label injections with aflibercept, the patient had improvement in lesion size, exudation, and visual acuity. Extensive workup yielded underlying immunocompromise because of the presence of anti-GM-CSF antibodies, likely predisposing her to disseminated Nocardiosis. The use of aflibercept in Nocardia chorioretinitis led to resolution of neovascular activity with visual recovery in a patient with disseminated Nocardiosis.
2016-11-01 | P200 A case report of disseminated nocardia infection in an adult with moderate lymphopenia
A 40-year-old male presented with disseminated nocardiosis in acute respiratory failure. He had a 20-year history of granulomatous lesions of the skin, which stabilized without treatment. Six months prior to presentation he developed cavitary lesions of the lungs. Bronchoscopy and biopsy confirmed Nocardia infection. Despite treatment with multiple culture-directed antibiotics, he developed a vertebral abscess, resulting in spinal cord compression and quadraplegia. He had no family history of immunodeficiency. Immune evaluation demonstrated decreased CD4+, CD8+, CD3+, and CD19+ cell counts. Functional studies revealed non-protective pneumococcal, diphtheria and tetanus serum IgG titers. Lymphocyte proliferation was absent to tetanus and low to candida antigens, PHA, ConA, and pokeweed mitogens. NK cell number, complement levels, and NADPH oxidative burst test were normal. HIV PCR test was negative. In collaboration with Dr. Holland at NIH, his serum was examined for autoantibodies to GM-CSF, IFN-y, IL-17A, which were undetectable. Although the defense mechanism against Nocardia is believed to be primarily cell-mediated, these results suggested an additional humoral component of disease, so the patient was treated with IVIG.
2009-11-02 | IgM but not IgG monoclonal anti-Nocardia brasiliensis antibodies confer protection against experimental actinomycetoma in BALB/c mice.
Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection.
2007-09-01 | The Potential Impact of Substitutive Therapy With Intravenous Immunoglobulin on the Outcome of Heart Transplant Recipients With Infections
Hypogammaglobulinemia has been proposed to be a risk factor for infection after heart transplantation (OHT). Infection is a leading cause of morbility and mortality among these patients. In a retrospective study we analyzed the impact of substitutive therapy with nonspecific intravenous immunoglobulin (IVIG) on the outcomes of heart transplant patients with infections. We analyzed the outcome of 123 consecutive heart transplant recipients in our center from June 1996 to November 2005. Their mean age was 53 years (range = 22 to 69 years), and the mean follow-up = 51 months, (range = 1 to 124 months). Twenty-nine patients with hypogammaglobulinemia (mean serum immunoglobulin G levels = 480 mg/dL) experienced severe infections due to cytomegalovirus (CMV) disease, n = 4; CMV disease + another infection, n = 6; CMV infection, n = 4; CMV infection + other infection, n = 3; pulmonary nocardiosis, n = 2; recurrent pneumonia, n = 2; clostridium-difficile-associated diarrhea, n = 2; pulmonary tuberculosis, n = 1; bacterial infections, n = 5. They were treated with IVIG (400 mg/kg every 21 days) with the goal to reach normal serum immunoglobulin G levels (>700 mg/dL). Overall (n = 123), a logistic regression analysis showed IVIG therapy to be associated with a decreased risk of death [odds ratio (OR) = 0.204, 95% confidence interval (CI) = 0.04 to 0.92, P = .03]. Among patients who developed infections during follow-up (n = 70), IVIG therapy was also associated with a lower risk of death (OR = 0.104, CI = 0.02 to 0.50, P = .0047). When we stratified patients with CMV disease (n = 24) according to the presence (n = 10) or absence (n = 14) of IVIG therapy, the mortality rate of IVIG-treated patients was 20% versus 71% for non-IVIG treated patients [OR = 0.06, CI = 0.0060 to 0.63, P = .01]. The use of nonspecific IVIG in OHT with hypogammaglobulinemia and infections might reduce the risk of death. Randomized studies in a larger cohort of patients are necessary to confirm these results.
other
2025-11-30 | A methionine sulfoxide reductase A homolog gene(msrA1)deficiency significantly attenuates the virulence of Nocardia seriolae.
Nocardia seriolae, a facultative intracellular pathogenic actinobacteria, is the primary aetiological agent of nocardiosis in both freshwater and marine fish. Methionine sulfoxide reductases (Msrs) has been shown to play important role in defensing against oxidative stress in many pathogenic bacteria. In present study, a methionine sulfoxide reductase A homolog gene (msrA1) was identified in the genome of N. seriolae and the gene deficient strain ΔmsrA1 was generated by homogenous recombination method. Growth curve showed the viable counts of ΔmsrA1 was significant more than its wild type (WT) stain during stationary phase. Compare with the WT strain, ΔmsrA1 showed significant more sensitive to hydrogen peroxide, but exhibited almost the same enduring ability to sodium hypochlorite. In a fish head kidney cell line (LYC-hK) model, the ΔmsrA1 strain displayed significantly decreased survival rates, alongside the weaken reactive oxygen species (ROS) and apoptosis inducing capacity, compare with its parental strain. Using largemouth bass as the infection model, the ΔmsrA1 strain showed significantly decreased bacterial loads in tissues and attenuated virulence, compare with the WT strain. Given the above, msrA1 was shown to be implicated in virulence of N. seriolae via enhancing the ability to resist the in vivo oxidative stress and survive inside host.
2025-04-06 | Genomic characteristics, virulence potential, antimicrobial resistance profiles, and phylogenetic insights into Nocardia cyriacigeorgica.
Nocardia cyriacigeorgica, an opportunistic pathogen, is increasingly implicated in human infections. This pathogen predominantly causes pulmonary infections, leading to acute, subacute, or chronic necrotizing suppurative lesions, in severe cases, may progress to disseminated infections. Effective clinical diagnosis, prevention, and treatment strategies require a thorough understanding of its biological characteristics and pathogenic mechanisms. However, despite the rising incidence of nocardial diseases, research on the pathogenicity of N. cyriacigeorgica remains limited, primarily focusing on case reports and epidemiological studies. This study aimed to provide a comprehensive analysis of the genomic features, phylogenetic relationships, antimicrobial resistance profiles, and candidate virulence factors of N. cyriacigeorgica strains to inform future investigations into its pathogenesis. Whole-genome sequencing was conducted on five N. cyriacigeorgica strains isolated from patients with pulmonary infection at our hospital. This analysis utilized a combination of second-generation Illumina HiSeq and third-generation PacBio sequencing technologies. Additionally, publicly available genomic data from 58 strains in the National Center Biotechnology Information database were integrated, resulting in a dataset of 63 genomes. These genomes were subjected to comparative genomic analyses, including phylogenetic reconstruction, pan-genome evaluation, and gene distribution assessments. Phylogenetic analysis identified five major clades within N. cyriacigeorgica. ANI analysis further subdivided clade B into five distinct subgroups. Pan-genome analysis revealed clade-specific orthogroups in the distribution of genes assigned to Clusters of Orthologous Groups, with clade A containing the highest number of clade-specific gene families. Comparative genomic analysis uncovered several potential pathogenic genes implicated in host cell invasion, phagosomal maturation arrest, and intracellular survival within macrophages, which were conserved across all analyzed strains. Notable differences in the distribution of enterobactin-encoding genes were observed among the clades. The mce3C gene also displayed variable distributions across clades; however, no correlation was established between its presence and strain source. Among the 63 strains, 27 were found to harbor both mce3C and mce4F genes, which were categorized into five distinct patterns. Furthermore, antibiotic resistance genes, including VanSO, VanRO, erm(O)-Irm, srmB, ermH, bcl, bla1, and cmIR, demonstrated clade-specific distribution patterns. Notably, the genes erm(O)-Irm, srmB, and ermH were associated with the isolation origin of the strains. This study provides a comprehensive evaluation of the genomic characteristics, potential virulence factors, antimicrobial resistance genes, and phylogenetic relationships of N. cyriacigeorgica. The findings offer valuable insights into the mechanisms underlying intracellular survival, replication within macrophages, and pathogen-host interactions in N. cyriacigeorgica infections. These results establish a foundation for future research into the pathogenesis and clinical management of N. cyriacigeorgica.
2025-03-10 | Evaluation of immunological effects of two DNA vaccines against Nocardia seriolae in hybrid snakehead.
Although DNA vaccines hold significant potential, their practical application in aquaculture remains limited. In both mammals and teleost fish, B cells, which recognize antigens and produce antibodies, play an important role in immunity. In this study, B-cell epitopes capable of inducing fish immunity from IS701 family transposase (IS701) and molybdopterin-dependent oxidoreductase (Mol) proteins of Nocardia seriolae were screened. PcDNA-IS701 and pcDNA-Mol recombinant plasmids were constructed. The results showed that two proteins possessed multiple B-cell epitopes, and both pcDNA-IS701 and pcDNA-Mol induced innate immunity and specific antibody responses, along with increased mRNA expression levels of genes encoding humoral (MHCIIα and CD4) and cell-mediated (MHCIα and CD8α) immunity. In addition, both pcDNA-IS701 and pcDNA-Mol strengthened the protection against N. seriolae infection, with immune protection rates of 45.06 % for IS701 and 61.04 % for Mol, respectively. In conclusion, pcDNA-IS701 and pcDNA-Mol are candidate DNA vaccines for nocardiosis in fish.
2024-08-12 | Development and evaluation of immunological effects of a DNA vaccine encoding phosphoketolase family protein against Nocardia seriolae in hybrid snakehead.
Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N. seriolae, encoding phosphoketolase (PK) family protein, was identified by in vivo-induced antigen technology. In the present study, the antigenic gene encoding PK family protein was analyzed by bioinformatics and further inserted into the eukaryotic expression vector pcDNA3.1-myc-his-A for DNA vaccine development. The immunological effects of pcDNA-PK DNA vaccine were assessed in hybrid snakehead (Channa maculata ♀ × Channa argus ♂), showing induction in several serum enzyme activity parameters (including LZM, SOD, ACP and AKP), increasing in specific-antibody IgM levels, as well as up-regulation in six immune-related genes (CD4, CD8α, TNFα, IL-1β, MHCIα and MHCIIα). Moreover, an immune-protection with a relative survival rate was provided at 53.82 % following artificial challenge with N. seriolae in vaccinated fish in comparison to the control group. In summary, these results indicate that pcDNA-PK DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, which may be applied in aquaculture to control fish nocardiosis.
2024-03-14 | Identifying the in vivo-induced antigenic genes is a strategy to develop DNA vaccine against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).
Nocardia seriolae has been identified as the causative agent of fish nocardiosis, resulting in serious economic losses in aquaculture. With an aim to screen potential candidates for vaccine development against N. seriolae, the in vivo-induced genes of N. seriolae in hybrid snakehead (Channa maculate ♀ × Channa argus ♂) model were profiled via in vivo-induced antigen technology (IVIAT) in the present study, and 6 in vivo-induced genes were identified as follows: IS701 family transposase (is701), membrane protein insertase YidC (yidC), ergothioneine biosynthesis glutamate-cysteine ligase (egtA), molybdopterin respectively-dependent oxidoreductase (mol), phosphoketolase family protein (Ppl), hypothetical protein 6747 (hp6747). Additionally, the yidC was inserted into eukaryotic expression vector pcDNA3.1-myc-his-A to construct a DNA vaccine named as pcDNA-YidC to evaluate immunoprotection in hybrid snakehead after artificial challenge with N. serioale. Results showed that the transcription of yidC was detected in spleen, trunk kidney, muscle and liver in vaccinated fish, suggesting that this antigenic gene can be recombinantly expressed in fish. Meanwhile, indexes of humoral immunity were evaluated in the vaccinated fish through assessing specific-antibody IgM and serum enzyme activities, including lysozyme (LZM), superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Quantitative real-time PCR analysis indicated that pcDNA-YidC DNA vaccine could notably enhance the expression of immune-related genes (CD4、CD8α、MHCIIα、TNFα、IL-1β and MHCIα) in 4 tissues (spleen, trunk kidney, muscle and liver) of the vaccinated fish. Finally, an immuno-protection with a relative survival rate of 65.71 % was displayed in vaccinated fish in comparison to the control groups. Taken together, these results indicate that pcDNA-YidC DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, indicating that IVIAT is a helpful strategy to screen the highly immunogenic antigens for vaccine development against fish nocardiosis.
small molecules
2026-08-16 | Disseminated Nocardia pseudobrasiliensis infection in a case of juvenile systemic lupus erythematosus on immunosuppressive therapy.
Nocardiosis is an uncommon infection that presents as a chronic, debilitating illness with radiographic manifestations simulating lung cancer or tuberculosis. Immunocompromised hosts may develop a fulminant disease resembling acute bacterial pneumonia or disseminated disease. We report a case of a juvenile lupus who developed disseminated Nocardia pseudobrasilienisis infection in form of necrotizing pneumonia, subcutaneous nodules and central nervous system (CNS) lesion in the right parietal lobe, following inadvertent hiking of steroids after a minor organ flare. This case was successfully treated with intravenous meropenem, amikacin, and oral cotrimoxazole therapy for 6 weeks which lead to resolution of pneumonia, and partial resolution of of the cutaneous and CNS lesion. As the patient was immunosuppressed, and had disseminated nocardiosis, we planned to put her on oral cotrimoxazole for the next 1 year.
2026-07-31 | Disseminated Nocardia farcinica with multiple cerebral abscesses in a patient receiving induction immunosuppression for autoimmune hepatitis: case report.
Nocardiosis is an opportunistic infection caused by aerobic, Gram-positive actinomycetes of the genus Nocardia that most often affects patients with impaired cell-mediated immunity, including those receiving corticosteroids or other immunosuppressive therapies. Disseminated disease frequently involves the central nervous system, where a systematic review reported an overall case fatality rate of 22.8%, and Nocardia farcinica is the most commonly identified species. We report a case of disseminated Nocardia farcinica with multiple cerebral abscesses in a patient receiving induction immunosuppressive therapy for autoimmune hepatitis. A 55-year-old man with a history of autoimmune hepatitis and occupational soil exposure presented with 4-5 week history of progressive cognitive impairment, dysarthria, and right upper extremity weakness. Two months earlier, he had been treated with high-dose corticosteroids and azathioprine and prescribed trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, which had been interrupted for an estimated 2-4 weeks before presentation during ongoing corticosteroid therapy. Upon admission, laboratory tests demonstrated neutrophil-predominant leukocytosis with lymphopenia, and liver function tests showed substantial improvement compared to his initial presentation of autoimmune hepatitis. Neuroimaging revealed multiple ring-enhancing intracerebral lesions with surrounding vasogenic edema. Stereotactic aspiration of a cerebral abscess and drainage of a concurrent retroperitoneal collection grew Nocardia farcinica, confirming disseminated nocardiosis. Antimicrobial therapy was transitioned to imipenem-cilastatin and TMP-SMX based on susceptibility testing. During infection management, azathioprine was paused, and prednisone was continued at a dose of 25 mg/day, followed by a biochemical autoimmune hepatitis flare requiring hepatology-guided monitoring. The patient demonstrated gradual neurologic improvement and was discharged to inpatient rehabilitation after an 18-day hospitalization. Disseminated nocardiosis should be considered for immunosuppressed patients with autoimmune hepatitis presenting with subacute neurological decline and ring-enhancing brain lesions, particularly during outpatient immunosuppression transitions when antimicrobial prophylaxis may be interrupted or incompletely reconciled. The patient demonstrated progressive neurological improvement and radiographic abscess reduction after 3 months of susceptibility-guided combination therapy, reinforcing the importance of early tissue diagnosis and neurosurgical intervention in this population.
2026-07-18 | Structure-based virtual screening identifies dicoumarol as a potent InhA inhibitor against Nocardia seriolae infection in largemouth bass (Micropterus salmoides)
Nocardiosis, caused by Nocardia seriolae , represents a critical bottleneck in the intensive aquaculture of largemouth bass ( Micropterus salmoides ), complicated by the pathogen's unique mycolic acid barrier and emerging multidrug resistance. To overcome the inefficiencies of traditional random screening, this study adopted a structure-based drug discovery strategy targeting InhA, the enoyl-acyl carrier protein reductase of the type II fatty acid synthase (FAS-II) pathway. Using AlphaFold 3-based structural modeling and high-throughput virtual screening, we identified dicoumarol (DIC) as a lead candidate. Biophysical assays, including isothermal titration calorimetry and fluorescence quenching, demonstrated high-affinity binding of DIC to the hydrophobic substrate-binding pocket of N. seriolae InhA (nsInhA). In vitro , DIC showed potent bactericidal activity and reduced intracellular bacterial loads in EPC cells. In vivo , dietary administration of DIC significantly improved survival and ameliorated granulomatous pathology in infected fish. Transcriptional analysis further showed reduced expression of the pro-inflammatory cytokines il1b and il6 in treated fish, consistent with an attenuated inflammatory burden during infection. Together, these findings support nsInhA as a druggable target and identify DIC as a promising therapeutic lead for the control of fish nocardiosis.
2026-07-16 | Disseminated nocardiosis in a Japanese raccoon dog (Nyctereutes procyonoides viverrinus).
A captive male Japanese raccoon dog died after self-mutilation by biting its tail and developing anorexia. At necropsy, ulceration of the tail root and pelvic region, an abdominal mass, multifocal nodules in the lungs, and thrombi in the heart were observed. Histopathological examinations revealed multifocal pyogranulomatous inflammation in the lungs, abdominal mass, spleen, brain, liver, and kidneys. Gram-positive bacterial aggregates were observed in the lungs, abdominal mass, and spleen. These organisms were partially acid-fast and periodic acid-Schiff-positive, and branching filaments were observed on Grocott's methenamine silver staining. Nocardia aobensis was identified in the abdominal mass by PCR and sequence analysis. These findings suggest that N. aobensis should be considered a potential cause of disseminated pyogranulomatous disease in animals.
2026-07-08 | Oral amoxicillin-clavulanate: an alternative treatment to refractory Nocardia keratitis-a case report.
Bacterial keratitis (bacterial corneal infection) is a serious, vision-threatening disease caused by a wide range of bacterial species. The gram-positive bacterium Nocardia spp. is increasingly recognized in keratitis, yet is particularly challenging to treat due to delayed diagnosis and limited efficacy of current ophthalmic therapeutics. Antimicrobial resistance among clinical Nocardia isolates is also rising, further complicating patient outcomes. Herein, we report a case of Nocardia amikacinitolerans keratitis, resistant to amikacin, ciprofloxacin, moxifloxacin, clarithromycin, and ceftriaxone, resulting in a complicated therapeutic course. A 53-year-old female presented with bacterial keratitis of the right eye, which over the course of 32 months progressed to scleritis (infection of the sclera) and a progressive, significant decrease in visual acuity to hand motion despite exhaustive topical and systemic antimicrobial therapies. While there is a general lack of efficacy of systemic therapies for bacterial keratitis, oral amoxicillin-clavulanate ultimately proved successful in resolving the infection. As Nocardia spp. ocular infections become more prevalent, this report underscores the highly virulent nature of this pathogen and provides insights into potential therapeutic modalities in the setting of multidrug resistance.
vaccines
2026-01-12 | Protective efficacy of the optimized GluB-MTAP fusion subunit vaccine against Nocardia seriolae infection in largemouth bass (Micropterus salmoides).
Nocardia seriolae is the predominant causative agent of piscine nocardiosis, exhibiting broad piscine host specificity along with prolonged latency periods and high mortality rates, thereby posing a severe threat to global fish health. However, reliably effective control measures remain limited. Subunit vaccines, derived from virulence factors or immunodominant proteins of the pathogen, are widely acknowledged as one of the most secure and potent strategies for mitigating disease outbreaks. Here we focused on five T7SS gene cluster proteins (MTAP, HP05, HP23, HP24, and VST) and the dominant N. seriolae secretory protein (GluB) as subunit vaccine candidates through whole-genome sequencing and HPLC-MS analysis, identifying GluB and MTAP as superior antigens through efficacy-based screening assessing immunogenicity, serum antibody titers, and protective efficacy. To further enhance the protective efficacy, we engineered a novel fusion antigen composed of GluB and MTAP. In Micropterus salmoides, immunization with the GluB-MTAP fusion antigen elicited robust defensive responses at 28 days post-immunization, characterized by enhanced antioxidant capacity and amplified inflammatory and humoral immunity. The fusion vaccine conferred significant protection against N. seriolae challenge with a relative percentage survival (RPS21d) of 70 %, achieving 72.3 % absolute survival compared to 8 % in controls, which represented absolute survival improvements of 6.3 % over GluB-monovalent (66 %) and 18.3 % over MTAP-monovalent immunization (54 %). Collectively, the GluB-MTAP subunit vaccine demonstrates substantial efficacy against nocardiosis in M. salmoides, providing a mechanistic platform for investigating Nocardia-host interplay. This study further establishes a rational framework for anti-Nocardia seriolae vaccine development and advances sustainable aquaculture disease control strategies.
2025-12-13 | Develop subunit vaccines against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂) using two resuscitation-promoting factors.
Fish nocardiosis is a bacterial disease epidemic in aquaculture, and Nocardia seriolae is its main pathogen. The prevention and treatment of N. seriolae infection face multiple challenges, such as the unclear mechanism of chronic infection, resistance to phagocyte killing, and unsatisfied therapeutic efficacy of antibiotics. Resuscitation-promoting factors (Rpfs) are widely found in gram-positive bacteria, and have been reported to be vaccine candidates against tuberculosis and nocardiosis. In this study, RpfB and RpfD of N. seriolae ZJ0503 were obtained by prokaryotic expression and combined with Freund's Incomplete Adjuvant (FIA) as subunit vaccines, respectively. Finally, their efficacy were accessed in hybrid snakehead. The results showed that the relative survival rates (RPS) of subunit vaccines RpfB + FIA and RpfD + FIA were 77.78 % and 70.37 %, respectively. Histopathological examination revealed that hybrid snakehead did not show cytotoxic activity after intraperitoneal injection of RpfB + FIA and RpfD + FIA vaccines. In addition, both RpfB + FIA and RpfD + FIA vaccines increased the activity of multiple nonspecific immune parameters such as LYZ, CAT, ACP, AKP and SOD in the fish serum. The production of specific antibodies (IgM) and the expression of immune-related genes (tnfα, il-1β, cd4, cd8α, mhciα and mhciiα) were significantly increased compared with the control groups. In summary, RpfB and RpfD subunit vaccines were safe and can effectively protect hybrid snakehead from N. seriolae infection, and are ideal vaccine candidates for preventing fish nocardiosis.
2025-11-17 | An isocitrate lyase gene-deleted strain of Nocardia seriolae in live attenuated vaccine development against fish nocardiosis.
Fish nocardiosis caused by Nocardia seriolae is a severe bacterial disease in aquaculture, causing significant economic losses. The effectiveness of antibiotics in dealing with nocardiosis induced by N. seriolae is not satisfactory. NsICL is a potential virulence factor in N. seriolae based on its crucial role in the glyoxylate cycle, its identity as a secreted protein, and its established role in virulence and intracellular survival in homologous pathogens such as Mycobacterium tuberculosis. so, the NS-ΔICL deletion strain was constructed to investigate its function. The NsICL gene was knocked out via homologous recombination to generate the mutant strain NS-ΔICL. Comparative analysis of morphology, growth, and virulence was performed between the mutant and wild-type strains. The NS-ΔICL strain was used to immunize hybrid snakehead (Channa maculata♀ × Channa argus♂), with immune responses evaluated through non-specific immune parameters, specific antibodies, and expression levels of immune-related genes. Protective efficacy was assessed by challenge tests. NS-ΔICL showed reduced virulence (LD50 = 2.60 × 105 cfu/fish) compared to the wild-type strain (LD50 = 4.32 × 104 cfu/fish). Immunized fish exhibited significantly higher levels of non-specific immune factors (AKP, ACP, POD, LZM) and specific IgM antibodies. Immune-related genes (MHCIα, CD4, IL-8) were upregulated in vaccinated fish. Relative percentage survival (RPS) was 77.03% in vaccinated fish after challenge tests, which indicating strong protective efficacy. The NS-ΔICL deletion strain was successfully constructed in this study. It can not only induce humoral and cellular immunity in fish but also effectively protect fish against N. seriolae infection. These results provide a foundation for the development of a live attenuated vaccine for treating fish nocardiosis.
2025-07-03 | Surface display of Nocardia seriolae HRP1 on Bacillus subtilis and its application as live vaccine for largemouth bass.
Micropterus salmoides, adaptable and fast-growing, is a major farmed fish in China. Intensive farming causes multiple diseases, especially hard-to-treat nocardiosis. Vaccines are an effective and safe prevention and control strategy against fish diseases. In this experiment, the highly antigenic HRP1 gene of Nocardia seriolae (N. seriolae) was displayed on the surface of Bacillus subtilis (B. subtilis), and an oral vaccine (HRP1-cotC-B. subtilis) was successfully developed. Immune responses in inoculated fish were tested intermittently over 5 weeks post-administration. Immune protection was evaluated via challenge test. Serological parameters testing showed that the activity of lysozyme and Glutathione Peroxidase (GSH-Px) were significantly increased at the 7th and 21st day post-immunization, and the activity of Alkaline Phosphatase was extremely increased compared to the control. qRT-PCR detection found that oral vaccine could significantly boost the IgM expression of spleen and head-kidney. The expression of spleen major histocompatibility complex (MHC) was enhanced, MHCII at the 7th, 21st day and MHCI at 35th day post-immunization respectively. MHCI has an increasing trend in the head-kidney. CD8 increased in both spleen and head-kidney at different stages of immunization. The inflammatory cytokine il-1β and anti-inflammatory cytokine TGF-β significantly increased in head-kidney at 35th day after immunization. The live bacterial vaccine altered the composition of the intestinal flora, demonstrated a decline in Firmicutes and an increase in Fusobacteria, and a significant decrease in Clostridium replaced by Cetobacterium at the genus level. Largemouth bass immunized with HRP1-cotC-B. subtilis spores exhibited a 18.18% relative survival rate after N. seriolae infection. In conclusion, this study developed a novel oral vaccine against N. seriolae in largemouth bass using B. subtilis spore surface display technology. Oral vaccination improves nonspecific immunity, induces innate and cellular immunity, strengthens bacterial resistance, and increases survival after pathogen infection. This offers an effective strategy for controlling fish nocardiosis in aquaculture.
2025-07-01 | Immunoinformatics-Guided Whole Proteome-Based Multi-Epitope mRNA Vaccine Design Against Nocardia asteroides Using Surface Antigens-A Subtractive Proteomics and Reverse Vaccinology Approach.
Nocardiosis is caused by the aerobic gram-positive bacterium Nocardia asteroides which is multidrug-resistant and primarily affects immunocompromised individuals. This study aims to design a broad-spectrum vaccine against Nocardiosis. We used subtractive proteomics and vaccinomics approaches to identify vaccine candidates to design an epitope-based vaccine against Nocardiosis. Four proteins in the outer membrane and extracellular regions were shortlisted on the basis of immunogenic parameters. T- and B-cell epitopes were predicted on the basis of IC50 < 200 nM, and a multi-epitope vaccine construct was designed using six overlapping CTL, HTL, and B-cell epitopes conjugated by appropriate linkers. A highly immunogenic adjuvant was integrated at the N-terminus of the multi-epitope vaccine to stimulate a robust immune response. The tertiary structure of the vaccine construct was predicted and validated with the 96% residues in the favorite region of the Ramachandran plot and a Z-score of -4.76. The proposed vaccine exhibited strong immunological and physicochemical features. High docking scores and strong binding energies of approximately -1051.9 to -1274.5 kcal/mol with human immune receptors ensured that the designed vaccine construct could induce potential immunogenic responses in the host immune system. The efficacy of the vaccine was evaluated by the immune simulation to determine the potential of the vaccine to simulate innate and adaptive immunity with the development of long-lasting memory immune cells. The molecular dynamic simulation of a 100 ns study was conducted to determine the structural stability and molecular function of the designed vaccine in the cellular microenvironment. In silico restriction cloning analysis determined the successful expression of the engineered vaccine construct in Escherichia coli plasmid with a size of 6323 bp. On the basis of the current study, we assume that the proposed vaccine is worthy of further in vitro in vivo and in vivo validations to ensure the efficacy of the engineered vaccine in this study.
proteins
2026-07-18 | Genetic and functional evidence links tgfbr2 to Nocardia seriolae resistance in spotted sea bass.
Spotted sea bass (Lateolabrax maculatus) is an economically important aquaculture species in China, but nocardiosis caused by Nocardia seriolae results in high mortality and economic losses. To investigate the genetic basis of disease resistance, two experimental populations are challenged and analyzed by genome-wide association studies (GWAS). We identify 112 SNPs, including 17 nonsynonymous variants in tgfbr2. Functional enrichment analysis highlights the TGF-β signaling and its related pathways. Structural analysis reveals that TGFBR2 is highly conserved, and mutations in the intracellular kinase domain may alter receptor conformation. Recombinant TGF-β1a modulated splenic lymphocytes transcription, upregulating foxp3b, il10 and smad7, while suppressing proinflammatory cytokines. The tgfbr2 mutation impaires downstream SMAD phosphorylation and reduces transcriptional activation of the foxp3b promoter. These results identify key genetic loci for resistance to N. seriolae and establish a mechanistic connection between TGF-β signaling and immune regulation, providing a foundation for molecular breeding of disease-resistant spotted sea bass.
2026-06-26 | Genome-wide identification of the cystatin gene family and functional characterization of cystatin B in flathead mullet (Mugil cephalus).
The cystatin superfamily is a class of endogenous cysteine protease inhibitors that play a key role in immune regulation and host defense. However, there remains a lack of genome-wide identification and functional studies of this gene family in the flathead mullet. Therefore, this study conducted a systematic identification of the cystatin gene family in flathead mullet at the genome-wide level and further characterized the function of McCysB (Mugil cephalus Cystatin B). The results revealed that seven cystatin genes were identified in the flathead mullet genome, which were classified into three subfamilies, namely stefins (type I), cystatins (type II), and kininogens (type III), based on phylogenetic analysis. based on phylogenetic analysis. Structural and conserved motif analysis indicated that all members contained a highly conserved cystatin domain, suggesting functional conservation during evolution. Chromosomal mapping revealed that these genes were unevenly distributed across four chromosomes and exhibited tandem duplication events. Collinearity analysis further revealed the evolutionary conservation of the cystatin gene locus in teleosts. Tissue expression profiling indicated that most McCys genes were highly expressed in immune-related tissues, with the most significant expression levels observed in the kidneys. Following infection with Vibrio harveyi, the expression level of McCysB was significantly upregulated, suggesting its potential involvement in the antimicrobial immune response. Furthermore, this study successfully expressed and purified the recombinant McCysB (rMcCysB), and the in vitro functional assays confirmed that this protein exhibited dose-dependent antibacterial activity against Staphylococcus aureus, Nocardia seriolae, Escherichia coli and V. harveyi, with a more pronounced inhibitory effect against Gram-negative bacteria. In summary, this study systematically elucidated the molecular characteristics, evolutionary patterns, and potential immunological roles of the cystatin gene family in the flathead mullet and revealed McCysB as a potential immune effector molecule, providing a candidate target for the development of antimicrobial strategies in aquaculture.
2026-03-13 | An Unusual Case of Cutaneous Nocardia cyriacigeorgica Infection Assuming the Appearance of Shingles.
Nocardia is an opportunistic organism that commonly infects the lungs of the immunocompromised and can cause disseminated infections. Diagnosis of Nocardia cyriacigeorgica is through culture and susceptibilities, aided by 16S rRNA sequencing. We report a case of a shingles-like rash eruption due to Nocardia cyriacigeorgica in a 69-year-old patient with a history of bilateral lung transplant.
2026-02-10 | Nocardiosis in Immunocompromised Hosts: A Retrospective, Single-Center Analysis of Clinical and Microbiological Determinants of Central Nervous System Involvement.
Immunocompromised patients are at risk of disseminated nocardiosis, which can involve the central nervous system. The factors mediating dissemination to the central nervous system in this patient population have not been fully characterized. This study aimed to identify patient and pathogen-related variables associated with a higher risk of central nervous system infection among immunocompromised patients with nocardiosis. Retrospective single-center analysis of all immunocompromised patients diagnosed with nocardiosis between 2013 and 2024. Patients without brain imaging were excluded from the analysis. A case-control analysis was conducted to compare patients with central nervous system involvement (cases) and those without (controls), examining demographic, immunosuppression-related, and pathogen-related variables through univariate analysis. A total of 54 patients were included in the study. The most common type of immunosuppression was solid organ transplantation (39%). The prevalence of central nervous system involvement was 30%. In univariate analysis, white, non-Hispanic patients and patients with bronchiectasis had lower odds of central nervous system involvement. In contrast, patients infected with Nocardia farcinica had higher odds of central nervous system involvement. Immunocompromised patients with nocardiosis who had brain involvement did not differ significantly from those without brain involvement in terms of immunosuppression-related factors. Instead, this difference appears to be explained by differences in the virulence of Nocardia species, particularly N. farcinica.
2026-01-30 | Disseminated Nocardia ignorata Infection with Splenic and Brain Involvement in Patient with Large B-Cell Lymphoma.
A 79-year-old man in the United States with large B-cell lymphoma and chronic obstructive pulmonary disease had disseminated Nocardia ignorata infection involving the brain and spleen. Despite antimicrobial therapy, he died from complications. This rare manifestation highlights the need to consider Nocardia in immunocompromised patients with central nervous system and abdominal lesions.
antibodies
2025-01-11 | Spontaneous remission of Pneumocystis jirovecii pneumonia followed by severe pulmonary nocardiosis in a patient with HIV infection: A case report.
We describe a rare case of spontaneous remission of Pneumocystis jirovecii pneumonia (PCP) in a 42-year-old patient with human immunodeficiency virus (HIV) infection, followed by severe pulmonary nocardiosis. To our knowledge, this is the first report of spontaneous remission of PCP in a completely untreated patient with HIV infection. The patient, a bisexual Japanese man, presented with fever and anorexia and had a history of non-compliance with antiretroviral therapy (ART) for 13 years. PCP was initially suspected on the basis of imaging and laboratory findings, but the patient refused further evaluation and treatment. Surprisingly, the evidence of PCP infection disappeared without intervention. Four months later, the patient was diagnosed with severe pulmonary nocardiosis caused by Nocardia beijingensis, which was confirmed by bronchoscopy and culture. Antibiotic therapy and ART resulted in significant clinical improvement. Based on this case, we propose that N. beijingensis infection may contribute to spontaneous remission of PCP, possibly through production of antimicrobial substances and induction of granulocyte-macrophage colony-stimulating factor. On the other hand, fluctuations in immune function, particularly variability in CD4+ T lymphocytes, may also contribute. This report highlights the complex interplay between opportunistic infections in immunocompromised patients. These findings may provide valuable insights into the management of PCP.
2024-08-02 | TREATMENT OF NOCARDIA CHORIORETINITIS-RELATED CHOROIDAL NEOVASCULARIZATION WITH AFLIBERCEPT: A CASE OF UNVEILED IMMUNOCOMPROMISE WITH ANTI-GM-CSF ANTIBODIES.
The purpose of this study was to describe a case of Nocardia chorioretinitis-related choroidal neovascularization in a patient with anti-GM-CSF antibodies with resolution of choroidal neovascularization and visual recovery after a series of intravitreal anti-vascular endothelial growth factor. This study is a case report. In this case, a 50-year-old woman, thought to be immunocompetent, presented with metamorphopsia and decreased visual acuity in the left eye in the setting of disseminated nocardiosis . She had evidence of a subfoveal Nocardia lesion with subretinal fluid and choroidal neovascularization. After a series of off-label injections with aflibercept, the patient had improvement in lesion size, exudation, and visual acuity. Extensive workup yielded underlying immunocompromise because of the presence of anti-GM-CSF antibodies, likely predisposing her to disseminated Nocardiosis. The use of aflibercept in Nocardia chorioretinitis led to resolution of neovascular activity with visual recovery in a patient with disseminated Nocardiosis.
2016-11-01 | P200 A case report of disseminated nocardia infection in an adult with moderate lymphopenia
A 40-year-old male presented with disseminated nocardiosis in acute respiratory failure. He had a 20-year history of granulomatous lesions of the skin, which stabilized without treatment. Six months prior to presentation he developed cavitary lesions of the lungs. Bronchoscopy and biopsy confirmed Nocardia infection. Despite treatment with multiple culture-directed antibiotics, he developed a vertebral abscess, resulting in spinal cord compression and quadraplegia. He had no family history of immunodeficiency. Immune evaluation demonstrated decreased CD4+, CD8+, CD3+, and CD19+ cell counts. Functional studies revealed non-protective pneumococcal, diphtheria and tetanus serum IgG titers. Lymphocyte proliferation was absent to tetanus and low to candida antigens, PHA, ConA, and pokeweed mitogens. NK cell number, complement levels, and NADPH oxidative burst test were normal. HIV PCR test was negative. In collaboration with Dr. Holland at NIH, his serum was examined for autoantibodies to GM-CSF, IFN-y, IL-17A, which were undetectable. Although the defense mechanism against Nocardia is believed to be primarily cell-mediated, these results suggested an additional humoral component of disease, so the patient was treated with IVIG.
2009-11-02 | IgM but not IgG monoclonal anti-Nocardia brasiliensis antibodies confer protection against experimental actinomycetoma in BALB/c mice.
Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection.
2007-09-01 | The Potential Impact of Substitutive Therapy With Intravenous Immunoglobulin on the Outcome of Heart Transplant Recipients With Infections
Hypogammaglobulinemia has been proposed to be a risk factor for infection after heart transplantation (OHT). Infection is a leading cause of morbility and mortality among these patients. In a retrospective study we analyzed the impact of substitutive therapy with nonspecific intravenous immunoglobulin (IVIG) on the outcomes of heart transplant patients with infections. We analyzed the outcome of 123 consecutive heart transplant recipients in our center from June 1996 to November 2005. Their mean age was 53 years (range = 22 to 69 years), and the mean follow-up = 51 months, (range = 1 to 124 months). Twenty-nine patients with hypogammaglobulinemia (mean serum immunoglobulin G levels = 480 mg/dL) experienced severe infections due to cytomegalovirus (CMV) disease, n = 4; CMV disease + another infection, n = 6; CMV infection, n = 4; CMV infection + other infection, n = 3; pulmonary nocardiosis, n = 2; recurrent pneumonia, n = 2; clostridium-difficile-associated diarrhea, n = 2; pulmonary tuberculosis, n = 1; bacterial infections, n = 5. They were treated with IVIG (400 mg/kg every 21 days) with the goal to reach normal serum immunoglobulin G levels (>700 mg/dL). Overall (n = 123), a logistic regression analysis showed IVIG therapy to be associated with a decreased risk of death [odds ratio (OR) = 0.204, 95% confidence interval (CI) = 0.04 to 0.92, P = .03]. Among patients who developed infections during follow-up (n = 70), IVIG therapy was also associated with a lower risk of death (OR = 0.104, CI = 0.02 to 0.50, P = .0047). When we stratified patients with CMV disease (n = 24) according to the presence (n = 10) or absence (n = 14) of IVIG therapy, the mortality rate of IVIG-treated patients was 20% versus 71% for non-IVIG treated patients [OR = 0.06, CI = 0.0060 to 0.63, P = .01]. The use of nonspecific IVIG in OHT with hypogammaglobulinemia and infections might reduce the risk of death. Randomized studies in a larger cohort of patients are necessary to confirm these results.
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2025-11-30 | A methionine sulfoxide reductase A homolog gene(msrA1)deficiency significantly attenuates the virulence of Nocardia seriolae.
Nocardia seriolae, a facultative intracellular pathogenic actinobacteria, is the primary aetiological agent of nocardiosis in both freshwater and marine fish. Methionine sulfoxide reductases (Msrs) has been shown to play important role in defensing against oxidative stress in many pathogenic bacteria. In present study, a methionine sulfoxide reductase A homolog gene (msrA1) was identified in the genome of N. seriolae and the gene deficient strain ΔmsrA1 was generated by homogenous recombination method. Growth curve showed the viable counts of ΔmsrA1 was significant more than its wild type (WT) stain during stationary phase. Compare with the WT strain, ΔmsrA1 showed significant more sensitive to hydrogen peroxide, but exhibited almost the same enduring ability to sodium hypochlorite. In a fish head kidney cell line (LYC-hK) model, the ΔmsrA1 strain displayed significantly decreased survival rates, alongside the weaken reactive oxygen species (ROS) and apoptosis inducing capacity, compare with its parental strain. Using largemouth bass as the infection model, the ΔmsrA1 strain showed significantly decreased bacterial loads in tissues and attenuated virulence, compare with the WT strain. Given the above, msrA1 was shown to be implicated in virulence of N. seriolae via enhancing the ability to resist the in vivo oxidative stress and survive inside host.
2025-04-06 | Genomic characteristics, virulence potential, antimicrobial resistance profiles, and phylogenetic insights into Nocardia cyriacigeorgica.
Nocardia cyriacigeorgica, an opportunistic pathogen, is increasingly implicated in human infections. This pathogen predominantly causes pulmonary infections, leading to acute, subacute, or chronic necrotizing suppurative lesions, in severe cases, may progress to disseminated infections. Effective clinical diagnosis, prevention, and treatment strategies require a thorough understanding of its biological characteristics and pathogenic mechanisms. However, despite the rising incidence of nocardial diseases, research on the pathogenicity of N. cyriacigeorgica remains limited, primarily focusing on case reports and epidemiological studies. This study aimed to provide a comprehensive analysis of the genomic features, phylogenetic relationships, antimicrobial resistance profiles, and candidate virulence factors of N. cyriacigeorgica strains to inform future investigations into its pathogenesis. Whole-genome sequencing was conducted on five N. cyriacigeorgica strains isolated from patients with pulmonary infection at our hospital. This analysis utilized a combination of second-generation Illumina HiSeq and third-generation PacBio sequencing technologies. Additionally, publicly available genomic data from 58 strains in the National Center Biotechnology Information database were integrated, resulting in a dataset of 63 genomes. These genomes were subjected to comparative genomic analyses, including phylogenetic reconstruction, pan-genome evaluation, and gene distribution assessments. Phylogenetic analysis identified five major clades within N. cyriacigeorgica. ANI analysis further subdivided clade B into five distinct subgroups. Pan-genome analysis revealed clade-specific orthogroups in the distribution of genes assigned to Clusters of Orthologous Groups, with clade A containing the highest number of clade-specific gene families. Comparative genomic analysis uncovered several potential pathogenic genes implicated in host cell invasion, phagosomal maturation arrest, and intracellular survival within macrophages, which were conserved across all analyzed strains. Notable differences in the distribution of enterobactin-encoding genes were observed among the clades. The mce3C gene also displayed variable distributions across clades; however, no correlation was established between its presence and strain source. Among the 63 strains, 27 were found to harbor both mce3C and mce4F genes, which were categorized into five distinct patterns. Furthermore, antibiotic resistance genes, including VanSO, VanRO, erm(O)-Irm, srmB, ermH, bcl, bla1, and cmIR, demonstrated clade-specific distribution patterns. Notably, the genes erm(O)-Irm, srmB, and ermH were associated with the isolation origin of the strains. This study provides a comprehensive evaluation of the genomic characteristics, potential virulence factors, antimicrobial resistance genes, and phylogenetic relationships of N. cyriacigeorgica. The findings offer valuable insights into the mechanisms underlying intracellular survival, replication within macrophages, and pathogen-host interactions in N. cyriacigeorgica infections. These results establish a foundation for future research into the pathogenesis and clinical management of N. cyriacigeorgica.
2025-03-10 | Evaluation of immunological effects of two DNA vaccines against Nocardia seriolae in hybrid snakehead.
Although DNA vaccines hold significant potential, their practical application in aquaculture remains limited. In both mammals and teleost fish, B cells, which recognize antigens and produce antibodies, play an important role in immunity. In this study, B-cell epitopes capable of inducing fish immunity from IS701 family transposase (IS701) and molybdopterin-dependent oxidoreductase (Mol) proteins of Nocardia seriolae were screened. PcDNA-IS701 and pcDNA-Mol recombinant plasmids were constructed. The results showed that two proteins possessed multiple B-cell epitopes, and both pcDNA-IS701 and pcDNA-Mol induced innate immunity and specific antibody responses, along with increased mRNA expression levels of genes encoding humoral (MHCIIα and CD4) and cell-mediated (MHCIα and CD8α) immunity. In addition, both pcDNA-IS701 and pcDNA-Mol strengthened the protection against N. seriolae infection, with immune protection rates of 45.06 % for IS701 and 61.04 % for Mol, respectively. In conclusion, pcDNA-IS701 and pcDNA-Mol are candidate DNA vaccines for nocardiosis in fish.
2024-08-12 | Development and evaluation of immunological effects of a DNA vaccine encoding phosphoketolase family protein against Nocardia seriolae in hybrid snakehead.
Fish nocardiosis is a chronic disease mainly caused by Nocardia seriolae, which occurs in a variety of economically cultured freshwater and marine fish. Studies have shown that DNA vaccine is an effective treatment to protect fish from bacterial infection. In our previous experiment, an in vivo-induced gene of N. seriolae, encoding phosphoketolase (PK) family protein, was identified by in vivo-induced antigen technology. In the present study, the antigenic gene encoding PK family protein was analyzed by bioinformatics and further inserted into the eukaryotic expression vector pcDNA3.1-myc-his-A for DNA vaccine development. The immunological effects of pcDNA-PK DNA vaccine were assessed in hybrid snakehead (Channa maculata ♀ × Channa argus ♂), showing induction in several serum enzyme activity parameters (including LZM, SOD, ACP and AKP), increasing in specific-antibody IgM levels, as well as up-regulation in six immune-related genes (CD4, CD8α, TNFα, IL-1β, MHCIα and MHCIIα). Moreover, an immune-protection with a relative survival rate was provided at 53.82 % following artificial challenge with N. seriolae in vaccinated fish in comparison to the control group. In summary, these results indicate that pcDNA-PK DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, which may be applied in aquaculture to control fish nocardiosis.
2024-03-14 | Identifying the in vivo-induced antigenic genes is a strategy to develop DNA vaccine against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).
Nocardia seriolae has been identified as the causative agent of fish nocardiosis, resulting in serious economic losses in aquaculture. With an aim to screen potential candidates for vaccine development against N. seriolae, the in vivo-induced genes of N. seriolae in hybrid snakehead (Channa maculate ♀ × Channa argus ♂) model were profiled via in vivo-induced antigen technology (IVIAT) in the present study, and 6 in vivo-induced genes were identified as follows: IS701 family transposase (is701), membrane protein insertase YidC (yidC), ergothioneine biosynthesis glutamate-cysteine ligase (egtA), molybdopterin respectively-dependent oxidoreductase (mol), phosphoketolase family protein (Ppl), hypothetical protein 6747 (hp6747). Additionally, the yidC was inserted into eukaryotic expression vector pcDNA3.1-myc-his-A to construct a DNA vaccine named as pcDNA-YidC to evaluate immunoprotection in hybrid snakehead after artificial challenge with N. serioale. Results showed that the transcription of yidC was detected in spleen, trunk kidney, muscle and liver in vaccinated fish, suggesting that this antigenic gene can be recombinantly expressed in fish. Meanwhile, indexes of humoral immunity were evaluated in the vaccinated fish through assessing specific-antibody IgM and serum enzyme activities, including lysozyme (LZM), superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Quantitative real-time PCR analysis indicated that pcDNA-YidC DNA vaccine could notably enhance the expression of immune-related genes (CD4、CD8α、MHCIIα、TNFα、IL-1β and MHCIα) in 4 tissues (spleen, trunk kidney, muscle and liver) of the vaccinated fish. Finally, an immuno-protection with a relative survival rate of 65.71 % was displayed in vaccinated fish in comparison to the control groups. Taken together, these results indicate that pcDNA-YidC DNA vaccine could boost strong immune responses in hybrid snakehead and show preferably protective efficacy against N. seriolae, indicating that IVIAT is a helpful strategy to screen the highly immunogenic antigens for vaccine development against fish nocardiosis.
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