RARE DISEASE
Amoebiasis due to free-living amoebae
Amoebiasis due to free-living amoebae
Amoebiasis due to free-living amoebae
Drug discovery
4
drugs
With orphan designations
Overview
Amoebiasis due to free-living amoebae is a rare but lethal parasitic disease caused by amphizoic protozoa (Acanthamoeba, Balamuthia, and Naegleria spp.) that naturally inhabit soil and water. These pathogens cause granulomatous amebic encephalitis (GAE), primary amebic meningoencephalitis (PAM), and keratitis, primarily affecting immunocompromised individuals or those exposed to contaminated water. Diagnosis is challenging due to nonspecific neurological symptoms and requires PCR/culture confirmation [2][5][15].
Categories: rare infectious diseases
Research Papers
96 drug discovery papers about Amoebiasis due to free-living amoebae, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
96 drug discovery papers about Amoebiasis due to free-living amoebae, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
vaccines
2024-12-30 | Transcriptomic profiling of "brain-eating amoeba" Naegleria fowleri infection in mice: the host and the protozoa perspectives.
The free-living amoeba Naegleria fowleri (NF) causes a rare but lethal parasitic meningoencephalitis (PAM) in humans. Currently, this disease lacks effective treatments and the specific molecular mechanisms that govern NF pathogenesis and host brain response remain unknown. To address some of these issues, we sought to explore naturally existing virulence diversity within environmental NF isolates. Herein, we purified two new NF environmental isolates (NF45 and NF1) and tested their in vivo virulence using experimental infection in mice. We found that NF45 was highly virulent (NF45_HV) compared with NF1 (low virulence, NF1_LV), based on in vivo amoeba growth kinetics and mouse survival. To identify underlying differences, we conducted RNA-seq and bioinformatics analyses from the infected mouse brains. Our results showed that NF1_LV and NF45_HV modulated the expression of their genes during mouse brain infection. Differentially expressed genes (DEGs) in NF1_LV were mostly involved in Translational protein, Protein-binding activity modulator, Protein modifying enzyme, while DEGs in NF45_HV were related to DNA metabolism, Cytoskeletal protein, Protein-binding activity modulator. Proteases (namely the virulence factor Cathepsin B) were upregulated in NF1_LV, while downregulated in NF45_HV. When analyzing the host response against infection by these two NF strains, enrichment analyses uncovered genes and mechanisms related to the host immune responses and nervous systems. We detected more DEGs in NF1_LV infected mice compared to NF45_HV, related to blood brain barrier leakage, immune cell recruitment, cytokine production (including IL-6, IFN-Ɣ and TNFα), inflammation of astrocytes and microglia, and oligodendrocyte and neurons degeneration. Increased expression of neuromotor-related genes such as Adam22, Cacnb4 and Zic1 (activated by NF1_LV infection) and ChAt (activated by NF45_LV infection) could explain PAM symptoms such as muscle weakness and seizures. Globally, our results showed that NF isolated from the environment can have different levels of virulence and differentially modulate their gene expression during brain infection. We also provided, for the first time, a comprehensive information for the molecular mechanisms of neuro-immune and host-pathogen interactions during PAM disease. As the host and the protozoa are strongly implicated in PAM lethality, new therapies targeting both the parasite, and the host should be considered to treat PAM infection.
2013-03-20 | Progress in the research on diagnosis and vaccines in amebiasis.
Entameba histolytica causes amebiasis, which includes both intestinal and extraintestinal amebiasis. E. histolytica causes 34 million to 50 million symptomatic cases of amebiasis worldwide every year, causing 40 thousand to 100 thousand deaths annually. E. histolytica, the pathogenic species of amebae is indistinguishable in its cyst and trophozoite stages from those of E. moshkovskii, a free-living ameba, and E. dispar, a non-invasive ameba, by microscopy, except in cases of invasive disease, where E. histolytica trophozoite may contain ingested red blood cells, but such a finding is rarely seen. This leads to a confusing scenario for the definite identification and differentiation of E. histolytica from E. moshkovskii and E. dispar by conventional microscopy, in the diagnosis of intestinal amebiasis. The advent of molecular methods such as multiplex PCR and real time PCR have facilitated a better and accurate diagnosis of E. histolytica, E. moshkovskii, and E. dispar in stool, urine, saliva, and other specimens. Multiplex PCR for the diagnosis of amebic liver abscess, using urine and saliva as clinical specimens, has been used, and the results have been encouraging. Real-time PCR is a new and a very attractive methodology for laboratory diagnosis of amebiasis, because of its characteristics that eliminate post-PCR analysis, leading to a shorter turnaround time. Microarray-based approaches represent an attractive diagnostic tool for the detection and identification of amebae in clinical and epidemiological investigations. Development of vaccines against amebiasis is still in its infancy. However, in recent years, progress has been made in the identification of possible vaccine candidates, the route of application, and the understanding of the immune response, which is required for protection against amebiasis. Thus, it is just a matter of time, and hopefully, amebiasis vaccine for human trials will be available in the next few years.
2005-03-11 | Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis.
The ocular surface is continuously exposed to potential pathogens, including free-living amoebae. Acanthamoeba species are among the most ubiquitous amoebae, yet Acanthamoeba keratitis is remarkably rare. The pathogenesis of Acanthamoeba keratitis is a complex, sequential process. Here we show that Acanthamoeba keratitis is profoundly affected by mannosylated proteins on the ocular surface, which stimulate the amoebae to elaborate a 133-kDa pathogenic protease. The mannose-induced protease (MIP133) mediates apoptosis of the corneal epithelium, facilitates corneal invasion, and degrades the corneal stroma. We show that contact lens wear upregulates mannosylated proteins on the corneal epithelium, stimulates MIP133 secretion, and exacerbates corneal disease. Corynebacterium xerosis, a constituent of the ocular flora, contains large amounts of mannose and is associated with Acanthamoeba keratitis. The present results show that amoebae exposed to C. xerosis produce increased amounts of MIP133 and more severe corneal disease. Oral immunization with MIP133 mitigates Acanthamoeba keratitis and demonstrates the feasibility of antidisease vaccines for pathogens that resist immune elimination.
1993-09-07 | [The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother].
Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization.
1992-03-16 | Pathogenic free-living amoebae.
Studies on pathogenic free-living amoebae performed in Korea were briefly reviewed. One strain of Naegleria fowleri was isolated from the sewage, and 3 strains of Acanthamoeba culbertsoni from a reservoir and the gill of fish. They were identified by morphological characteristics. Three strains among the 4 were experimentally proved pathogenic to cause primary amoebic meningoencephalitis in mice. The virulence of N. fowleri depended upon various factors such as strain, weight and sex of mice, and number of the inoculated amoebae. A. culbertsoni was found to retain cytolytic activities which were related to the pathogenicity. Also these amoebae were demonstrated to harbour the activities of acid phosphatase, peroxidase and ATPase. There is one case record of systemic Acanthamoeba infection in Korea, proved at autopsy. Cellular or humoral responses to these amoebae have been studied in vitro or in vivo. Immunization could reduce the mortality of experimentally infected mice.
proteins
2024-02-01 | Lactase can target cellular differentiation of Acanthamoeba castellanii belonging to the T4 genotype.
The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.
2021-08-05 | Entamoeba histolyticadevelops resistance to complement deposition and lysis after acquisition of human complement regulatory proteins through trogocytosis
ABSTRACT Entamoeba histolytica is the cause of amoebiasis. The trophozoite (amoeba) form of this parasite is capable of invading the intestine, and can disseminate through the bloodstream to other organs. The mechanisms that allow amoebae to evade complement deposition during dissemination have not been well characterized. We previously discovered a novel complement-evasion mechanism employed by E. histolytica . E. histolytica ingests small bites of living human cells in a process termed trogocytosis. We demonstrated that amoebae were protected from lysis by human serum following trogocytosis of human cells, and that amoebae acquired and displayed human membrane proteins from the cells they ingested. Here, we aimed to define how amoebae are protected from complement lysis after performing trogocytosis. We found that amoebae were protected from complement lysis after ingestion of both human Jurkat T cells and red blood cells, and that the level of protection correlated with the amount of material ingested. Trogocytosis of human cells led to a reduction in deposition of C3b on the surface of amoebae. We asked whether display of human complement regulators is involved in amoebic protection, and found that CD59 was displayed by amoebae after trogocytosis. Deletion of a single complement regulatory protein, CD59 or CD46, from Jurkat cells was not sufficient to alter amoebic protection from lysis, suggesting that multiple, redundant complement regulators mediate amoebic protection. However, exogeneous expression of CD46 or CD55 in amoebae was sufficient to confer protection from lysis. These studies shed light on a novel strategy for immune evasion by a pathogen. IMPORTANCE Entamoeba histolytica is the cause of amoebiasis, a diarrheal disease of global importance. While infection is often asymptomatic, the trophozoite (amoeba) form of this parasite is capable of invading and ulcerating the intestine, and can disseminate through the bloodstream to other organs. Understanding how E. histolytica evades the complement system during dissemination is of great interest. Here we demonstrate for the first time that amoebae that have performed trogocytosis (nibbling of human cells) resist deposition of the complement protein C3b. Amoebae that have performed trogocytosis display the complement regulatory protein CD59. Overall, our studies suggest that acquisition and display of multiple, redundant complement regulators is involved in amoebic protection from complement lysis. These findings shed light on a novel strategy for immune evasion by a pathogen. Since other parasites use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.
2016-02-10 | Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.
Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report on the structure of cellulose and cellulases, as well as known cellulose degradation mechanisms with an eye to target the Acanthamoeba cyst wall. The disruption of the cyst wall will make amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very least inhibition of the excystment process will impede infection recurrence, as we bring these promising drug targets into focus so that they can be explored to their fullest.
2003-08-05 | Enhanced killing of Acanthamoeba cysts with a plant peroxidase-hydrogen peroxide-halide antimicrobial system.
The activity of H(2)O(2) against the resistant cyst stage of the pathogenic free-living amoeba Acanthamoeba was enhanced by the addition of KI and either horseradish peroxidase or soybean peroxidase or, to a lesser degree, lactoperoxidase. This resulted in an increase in the cysticidal activity of 3% (wt/vol) H(2)O(2), and there was >3-log killing in 2 h, compared with the 6 h required for comparable results with the peroxide solution alone (P < 0.05). With 2% H(2)O(2), enhancement was observed at all time points (P < 0.05), and total killing of the cyst inoculum occurred at 4 h, compared with 6 h for the peroxide alone. The activity of sublethal 1% H(2)O(2) was enhanced to give 3-log killing after 8 h of exposure (P < 0.05). No enhancement was obtained when KCl or catalase was used as a substitute in the reaction mixtures. The H(2)O(2) was not neutralized in the enhanced system during the experiments. However, in the presence of a platinum disk used to neutralize H(2)O(2) in contact lens care systems, the enhanced 2% H(2)O(2) system gave 2.8-log killing after 6 h or total cyst killing by 8 h, and total neutralization of the H(2)O(2) occurred by 4 h. In contrast, 2% H(2)O(2) alone resulted in <0.8-log killing of cysts in the presence of the platinum disk due to rapid (<1 h) neutralization of the peroxide. Our observations could result in significant improvement in the efficacy of H(2)O(2) contact lens disinfection systems against Acanthamoeba cysts and prevention of acanthamoeba keratitis.
2000-02-25 | The increasing importance of Acanthamoeba infections.
Free-living amebae belonging to the genus Acanthamoeba are the causative agents of granulomatous amebic encephalitis, a chronic progressive disease of the central nervous system, and of amebic keratitis, a chronic eye infection. Granulomatous amebic encephalitis occurs more frequently in immunocompromised patients while keratitis occurs in healthy individuals. The recent increased incidence in Acanthamoeba infections is due in part to infection in patients with acquired immune deficiency syndrome, while that for keratitis is due to the increased use of contact lenses. Understanding the mechanism of host resistance to Acanthamoeba is essential since the amebae are resistant to many therapeutic agents. Studies in our laboratory as well as from others have demonstrated that macrophages from immunocompetent animals are important effector cells against Acanthamoeba. We have demonstrated also that microglial cells, resident macrophages of the brain, elicit cytokines in response to A. castellanii. Neonatal rat cortical microglia from Sprague-Dawley rats co-cultured with A. castellanii produced mRNA for the inflammatory cytokines, interleukin 1alpha, interleukin 1beta, and tumor necrosis factor alpha. In addition, scanning and transmission electron microscopy revealed that microglia ingested and destroyed A. castellanii in vitro. These results implicate macrophages as playing an effector role against Acanthamoeba and suggest immune modulation as a potential alternative therapeutic mode of treatment for these infections.
small molecules
2026-03-28 | Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence.
Devastating or nearly invariably fatal infections caused by free-living amoebae (FLA), including Acanthamoeba keratitis (AK), granulomatous amoebic encephalitis (GAE), and primary amoebic meningoencephalitis (PAM), remain a significant public health concern, driven by increasing case numbers, geographic expansion, and the lack of approved, effective, and safe treatments. Despite decades of research, no new drugs have been successfully approved, highlighting the severe limitations of de novo drug development for these infections, particularly for GAE and PAM, largely due to the challenges of conducting clinical trials for these rare and rapidly lethal diseases. In this context, drug repurposing represents a cost-effective and promising strategy to accelerate therapeutic advances and overcome key bottlenecks of conventional drug development. Accordingly, we conducted a systematic review of in vitro studies and animal models of AK, GAE, and PAM reported in indexed databases to identify promising drug repurposing candidates against FLA infections. After screening 23,624 records, 112 studies were included in the analysis. Overall, 2726 drugs and drug combinations, spanning 865 pharmacological classes and approved for 565 therapeutic indications, were assessed for their repurposing potential. Among these, 166 compounds showed substantial trophocidal activity (≥IC50) at potentially translatable concentrations (≤10 µM), including six with additional cysticidal activity. In vitro, four compounds were active against Balamuthia mandrillaris, 44 against Acanthamoeba spp. (three cysticidal), and 115 against Naegleria spp. (three cysticidal). In in vivo studies, sulfadiazine and rifampicin were effective as preventive or early monotherapies for GAE. For AK, the combination of polyhexamethylene biguanide, neomycin, and atropine, as well as voriconazole and nitazoxanide monotherapies, showed the greatest promise. In PAM, azithromycin alone or in combination with amphotericin B emerged as the most promising therapeutic options. Further studies are required to advance the clinical translatability of these findings. To the best of our knowledge, this work provides the first comprehensive and integrated synthesis of repurposable drug candidates against FLA infections.
2026-01-25 | Different roads to the brain: A brief overview of divergent pathways and convergent mechanisms in amoebic neuroinvasion.
Free-living amoebae such as Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri are opportunistic protists capable of causing devastating infections of the central nervous system. Although these organisms differ in ecology, morphology, and clinical progression, they converge on shared strategies that enable adhesion, immune evasion, and neuroinvasion. Here, we briefly present a comparative analysis of their routes of entry, molecular determinants, and neuropathogenic mechanisms with an eye to understand parallel and divergent pathways. A complete understanding of shared and distinct mechanisms can inform translational advances, including organoid-based modelling, multi-omics biomarker discovery, and therapeutic targeting of conserved host-pathogen signalling pathways.
2025-12-10 | Drug susceptibility of a clinical isolate of Balamuthia mandrillaris, a pathogenic free-living amoeba.
Balamuthia amoebic encephalitis (BAE) is a highly fatal infection caused by Balamuthia mandrillaris, an amoeba that lives in soil and water. In Thailand, three fatal cases of BAE have been documented, but no survivors have been reported, raising questions about current treatment regimens. Previous drug repurposing studies reveal some potent pharmacological compounds, but the drug susceptibility of the clinical isolate of pathogenic amoeba remains variable. Given the success in isolating B. mandrillaris from the human biopsied brain, this study aims to assess the amoebicidal effect of several previously repurposed drugs and suggested therapies for BAE. The trophozoites of a new clinical isolate, the KM-20 strain, were exposed to 12 compounds, including pentamidine, the most widely used antiprotozoal drug, and nitroxoline, the recent radical cure for BAE. The amoebicidal effect was assessed using the ATP level as a cell survival biomarker. The circularity and surface area of the cells were used as recrudescence indicators. Among all drugs tested, nitroxoline is the most potent amoebicidal drug without recrudescence. Topical antiseptic agents caused amoeba lysis at all doses tested, suggesting potential use for cutaneous balamuthiasis. Compared with two laboratory-adapted V039 and PRA-291 strains, the KM-20 isolate had reduced drug susceptibility to all of the tested compounds, suggesting strain dependency of amoebicidal activity. This study provides drug susceptibility data against a novel and geographically diverse clinical isolate of B. mandrillaris to assist in prioritizing anti-Balamuthia agents for further drug development testing, followed by in vivo efficacy testing animal models before clinical trials and drug repurposing.
2025-10-29 | A Review on Phytochemistry, Ethnopharmacology, and Antiparasitic Potential of Mangifera indica L.
Parasitic infections remain a major global health challenge, particularly in resource-limited settings where they are closely tied to poverty and inadequate sanitation. The increasing emergence of drug resistance and the limited accessibility of current therapies highlight the urgent need for novel, safe, and affordable alternatives. Mangifera indica L. (mango), a widely cultivated fruit tree deeply rooted in traditional medicine, has long been used to treat conditions symptomatic of parasitic diseases, including fever, diarrhea, and dysentery. Phytochemical investigations have revealed a rich spectrum of bioactive compounds, notably mangiferin, phenolic compounds and terpenoids, which exhibit antimicrobial, antioxidant, and immunomodulatory activities. This review critically synthesizes evidence on the antiparasitic potential of M. indica against protozoa, such as Plasmodium, Leishmania, Trypanosoma, Toxoplasma gondii, Entamoeba histolytica, and free-living amoebae, as well as helminths. Strongest evidence exists for malaria and helminth infections, where both crude extracts and isolated compounds demonstrated significant activity in vitro and in vivo. Encouraging but limited findings are available for leishmaniasis and trypanosomiasis, while data on toxoplasmosis and amoebiasis remain largely speculative. Variations in efficacy across studies are influenced by plant parts and extraction methods, with ethanolic extracts and mangiferin often showing superior results. Despite promising findings, mechanistic studies, standardized methodologies, toxicological evaluations, and clinical trials are scarce. Future research should focus on elucidating molecular mechanisms, exploring synergistic interactions with existing drugs, and leveraging advanced delivery systems to enhance bioavailability.
2025-09-05 | Ultrastructural characterization and pathogenicity of Allovohlkamfia spelaea in a murine model: Neuropulmonary infections and therapeutic potential of ellagic acid.
Allovahlkampfia spelaea (A. spelaea) is a free-living amoeba that has recently been recognized to cause Acanthamoeba-like keratitis, the treatment of which is complex. The pathogenic potential of Allovahlkampfia spp. remains unexplored. This study characterized A. spelaea through ultrastructural morphological analysis and investigated the pathogenic potential of the A. spelaea strain KS1, which was isolated from a patient with keratitis, in a murine model, with a focus on neuro-pulmonary infections. Additionally, this study assessed the therapeutic effectiveness of ellagic acid (EA) against tissue damage caused by amoebic infections. Immunosuppressed male Wister rats were intranasally inoculated with A. spelaea trophozoites (1 × 106/ml) and divided into control, infected untreated, and infected treated (50 mg/kg EA daily) groups. Histopathological and ultrastructural analyses of brain and lung tissues were conducted by scanning and transmission electron microscopy. Additionally, the therapeutic effects of EA were assessed via comparative tissue pathology. A. spelaea infection induced A. spelaea-induced neural lesions resembling granulomatous amoebic encephalitis (GAE) in the brain, which was characterized by gliosis, vasculitis, and necrosis, in addition to severe pulmonary damage, including suppurative bronchopneumonia and abscesses. Trophozoites presented with pseudopodia, acanthopodia, and amoebostomes, whereas cysts presented with double-layered walls. EA-treated rats presented nearly normal brain and lung histology, with reduced inflammation and gliosis, highlighting the anti-inflammatory and antioxidant properties of EA. This study highlights the neurotropic and pulmonary pathogenicity of A. spelaea, with ultrastructures parallel to those of Vahlkampfia spp. and Acanthamoeba spp. Ellagic acid significantly reduces infection-induced damage, underscoring its potential as a therapeutic agent for infections caused by free-living amoebae.
gene therapies
2024-10-03 | Comparative genomic analysis of Acanthamoeba from different sources and horizontal transfer events of antimicrobial resistance genes.
Acanthamoeba species are among the most common free-living amoeba and ubiquitous protozoa, mainly distributed in water and soil, and cause Acanthamoeba keratitis (AK) and severe visual impairment in patients. Although several studies have reported genomic characteristics of Acanthamoeba, limited sample sizes and sources have resulted in an incomplete understanding of the genetic diversity of Acanthamoeba from different sources. While endosymbionts exert a significant influence on the phenotypes of Acanthamoeba, including pathogenicity, virulence, and drug resistance, the species diversity and functional characterization remain largely unexplored. Herein, our study sequenced and analyzed the whole genomes of 19 Acanthamoeba pathogenic strains that cause AK, and by integrating publicly available genomes, we sampled 29 Acanthamoeba strains from ocular, environmental, and other sources. Combined pan-genomic and comparative functional analyses revealed genetic differences and evolutionary relationships among the different sources of Acanthamoeba, as well as classification into multiple functional groups, with ocular isolates in particular showing significant differences that may account for differences in pathogenicity. Phylogenetic and rhizome gene mosaic analyses of ocular Acanthamoeba strains suggested that genomic exchanges between Acanthamoeba and endosymbionts, particularly potential antimicrobial resistance genes trafficking including the adeF, amrA, and amrB genes exchange events, potentially contribute to Acanthamoeba drug resistance. In conclusion, this study elucidated the adaptation of Acanthamoeba to different ecological niches and the influence of gene exchange on the evolution of ocular Acanthamoeba genome, guiding the clinical diagnosis and treatment of AK and laying a theoretical groundwork for developing novel therapeutic approaches. Acanthamoeba causes a serious blinding keratopathy, Acanthamoeba keratitis, which is currently under-recognized by clinicians. In this study, we analyzed 48 strains of Acanthamoeba using a whole-genome approach, revealing differences in pathogenicity and function between strains of different origins. Horizontal transfer events of antimicrobial resistance genes can help provide guidance as potential biomarkers for the treatment of specific Acanthamoeba keratitis cases.
vaccines
2024-12-30 | Transcriptomic profiling of "brain-eating amoeba" Naegleria fowleri infection in mice: the host and the protozoa perspectives.
The free-living amoeba Naegleria fowleri (NF) causes a rare but lethal parasitic meningoencephalitis (PAM) in humans. Currently, this disease lacks effective treatments and the specific molecular mechanisms that govern NF pathogenesis and host brain response remain unknown. To address some of these issues, we sought to explore naturally existing virulence diversity within environmental NF isolates. Herein, we purified two new NF environmental isolates (NF45 and NF1) and tested their in vivo virulence using experimental infection in mice. We found that NF45 was highly virulent (NF45_HV) compared with NF1 (low virulence, NF1_LV), based on in vivo amoeba growth kinetics and mouse survival. To identify underlying differences, we conducted RNA-seq and bioinformatics analyses from the infected mouse brains. Our results showed that NF1_LV and NF45_HV modulated the expression of their genes during mouse brain infection. Differentially expressed genes (DEGs) in NF1_LV were mostly involved in Translational protein, Protein-binding activity modulator, Protein modifying enzyme, while DEGs in NF45_HV were related to DNA metabolism, Cytoskeletal protein, Protein-binding activity modulator. Proteases (namely the virulence factor Cathepsin B) were upregulated in NF1_LV, while downregulated in NF45_HV. When analyzing the host response against infection by these two NF strains, enrichment analyses uncovered genes and mechanisms related to the host immune responses and nervous systems. We detected more DEGs in NF1_LV infected mice compared to NF45_HV, related to blood brain barrier leakage, immune cell recruitment, cytokine production (including IL-6, IFN-Ɣ and TNFα), inflammation of astrocytes and microglia, and oligodendrocyte and neurons degeneration. Increased expression of neuromotor-related genes such as Adam22, Cacnb4 and Zic1 (activated by NF1_LV infection) and ChAt (activated by NF45_LV infection) could explain PAM symptoms such as muscle weakness and seizures. Globally, our results showed that NF isolated from the environment can have different levels of virulence and differentially modulate their gene expression during brain infection. We also provided, for the first time, a comprehensive information for the molecular mechanisms of neuro-immune and host-pathogen interactions during PAM disease. As the host and the protozoa are strongly implicated in PAM lethality, new therapies targeting both the parasite, and the host should be considered to treat PAM infection.
2013-03-20 | Progress in the research on diagnosis and vaccines in amebiasis.
Entameba histolytica causes amebiasis, which includes both intestinal and extraintestinal amebiasis. E. histolytica causes 34 million to 50 million symptomatic cases of amebiasis worldwide every year, causing 40 thousand to 100 thousand deaths annually. E. histolytica, the pathogenic species of amebae is indistinguishable in its cyst and trophozoite stages from those of E. moshkovskii, a free-living ameba, and E. dispar, a non-invasive ameba, by microscopy, except in cases of invasive disease, where E. histolytica trophozoite may contain ingested red blood cells, but such a finding is rarely seen. This leads to a confusing scenario for the definite identification and differentiation of E. histolytica from E. moshkovskii and E. dispar by conventional microscopy, in the diagnosis of intestinal amebiasis. The advent of molecular methods such as multiplex PCR and real time PCR have facilitated a better and accurate diagnosis of E. histolytica, E. moshkovskii, and E. dispar in stool, urine, saliva, and other specimens. Multiplex PCR for the diagnosis of amebic liver abscess, using urine and saliva as clinical specimens, has been used, and the results have been encouraging. Real-time PCR is a new and a very attractive methodology for laboratory diagnosis of amebiasis, because of its characteristics that eliminate post-PCR analysis, leading to a shorter turnaround time. Microarray-based approaches represent an attractive diagnostic tool for the detection and identification of amebae in clinical and epidemiological investigations. Development of vaccines against amebiasis is still in its infancy. However, in recent years, progress has been made in the identification of possible vaccine candidates, the route of application, and the understanding of the immune response, which is required for protection against amebiasis. Thus, it is just a matter of time, and hopefully, amebiasis vaccine for human trials will be available in the next few years.
2005-03-11 | Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis.
The ocular surface is continuously exposed to potential pathogens, including free-living amoebae. Acanthamoeba species are among the most ubiquitous amoebae, yet Acanthamoeba keratitis is remarkably rare. The pathogenesis of Acanthamoeba keratitis is a complex, sequential process. Here we show that Acanthamoeba keratitis is profoundly affected by mannosylated proteins on the ocular surface, which stimulate the amoebae to elaborate a 133-kDa pathogenic protease. The mannose-induced protease (MIP133) mediates apoptosis of the corneal epithelium, facilitates corneal invasion, and degrades the corneal stroma. We show that contact lens wear upregulates mannosylated proteins on the corneal epithelium, stimulates MIP133 secretion, and exacerbates corneal disease. Corynebacterium xerosis, a constituent of the ocular flora, contains large amounts of mannose and is associated with Acanthamoeba keratitis. The present results show that amoebae exposed to C. xerosis produce increased amounts of MIP133 and more severe corneal disease. Oral immunization with MIP133 mitigates Acanthamoeba keratitis and demonstrates the feasibility of antidisease vaccines for pathogens that resist immune elimination.
1993-09-07 | [The effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mother].
Acanthamoeba culbertsoni is a pathogenic free-living amoeba causing primary amoebic meningoencephalitis (PAME) in human and mouse. Several reports on the immune responses in mice with this amoebic infection have been published, but the effects of transferred passive immunity on the active immunization in offspring mice have not been demonstrated. This experiment was done to observe the effect of active immunization with Acanthamoeba culbertsoni in mice born to immune mothers. Acanthamoeba culbertsoni was cultured in the CGV medium axenically. Female BALB/c mice weighing about 20g were immunized through the intraperitoneal injection of Acanthamoeba culbertsoni trophozoites 1 x 10(6) each three times at the interval of one week. Offspring mice were immunized two times. The mice were inoculated intranasally with 1 x 10(4) trophozoites under secobarbital anesthesia. There was a statistical difference in mortality between the transferred immunity group and the active immunization group. Statistical differences were not demonstrated in antibody titer between both groups. But L3T4+ T cell/Ly2+ T cell ratio was increased in the transferred immunity group more than active immunization group of the offspring mice at the age of 5 weeks. There was no differences statistically in mortality between both groups. It was recognized that active immunization in offspring mice born to immune mother could modulate the immune status according to the time of immunization.
1992-03-16 | Pathogenic free-living amoebae.
Studies on pathogenic free-living amoebae performed in Korea were briefly reviewed. One strain of Naegleria fowleri was isolated from the sewage, and 3 strains of Acanthamoeba culbertsoni from a reservoir and the gill of fish. They were identified by morphological characteristics. Three strains among the 4 were experimentally proved pathogenic to cause primary amoebic meningoencephalitis in mice. The virulence of N. fowleri depended upon various factors such as strain, weight and sex of mice, and number of the inoculated amoebae. A. culbertsoni was found to retain cytolytic activities which were related to the pathogenicity. Also these amoebae were demonstrated to harbour the activities of acid phosphatase, peroxidase and ATPase. There is one case record of systemic Acanthamoeba infection in Korea, proved at autopsy. Cellular or humoral responses to these amoebae have been studied in vitro or in vivo. Immunization could reduce the mortality of experimentally infected mice.
proteins
2024-02-01 | Lactase can target cellular differentiation of Acanthamoeba castellanii belonging to the T4 genotype.
The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.
2021-08-05 | Entamoeba histolyticadevelops resistance to complement deposition and lysis after acquisition of human complement regulatory proteins through trogocytosis
ABSTRACT Entamoeba histolytica is the cause of amoebiasis. The trophozoite (amoeba) form of this parasite is capable of invading the intestine, and can disseminate through the bloodstream to other organs. The mechanisms that allow amoebae to evade complement deposition during dissemination have not been well characterized. We previously discovered a novel complement-evasion mechanism employed by E. histolytica . E. histolytica ingests small bites of living human cells in a process termed trogocytosis. We demonstrated that amoebae were protected from lysis by human serum following trogocytosis of human cells, and that amoebae acquired and displayed human membrane proteins from the cells they ingested. Here, we aimed to define how amoebae are protected from complement lysis after performing trogocytosis. We found that amoebae were protected from complement lysis after ingestion of both human Jurkat T cells and red blood cells, and that the level of protection correlated with the amount of material ingested. Trogocytosis of human cells led to a reduction in deposition of C3b on the surface of amoebae. We asked whether display of human complement regulators is involved in amoebic protection, and found that CD59 was displayed by amoebae after trogocytosis. Deletion of a single complement regulatory protein, CD59 or CD46, from Jurkat cells was not sufficient to alter amoebic protection from lysis, suggesting that multiple, redundant complement regulators mediate amoebic protection. However, exogeneous expression of CD46 or CD55 in amoebae was sufficient to confer protection from lysis. These studies shed light on a novel strategy for immune evasion by a pathogen. IMPORTANCE Entamoeba histolytica is the cause of amoebiasis, a diarrheal disease of global importance. While infection is often asymptomatic, the trophozoite (amoeba) form of this parasite is capable of invading and ulcerating the intestine, and can disseminate through the bloodstream to other organs. Understanding how E. histolytica evades the complement system during dissemination is of great interest. Here we demonstrate for the first time that amoebae that have performed trogocytosis (nibbling of human cells) resist deposition of the complement protein C3b. Amoebae that have performed trogocytosis display the complement regulatory protein CD59. Overall, our studies suggest that acquisition and display of multiple, redundant complement regulators is involved in amoebic protection from complement lysis. These findings shed light on a novel strategy for immune evasion by a pathogen. Since other parasites use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.
2016-02-10 | Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.
Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report on the structure of cellulose and cellulases, as well as known cellulose degradation mechanisms with an eye to target the Acanthamoeba cyst wall. The disruption of the cyst wall will make amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very least inhibition of the excystment process will impede infection recurrence, as we bring these promising drug targets into focus so that they can be explored to their fullest.
2003-08-05 | Enhanced killing of Acanthamoeba cysts with a plant peroxidase-hydrogen peroxide-halide antimicrobial system.
The activity of H(2)O(2) against the resistant cyst stage of the pathogenic free-living amoeba Acanthamoeba was enhanced by the addition of KI and either horseradish peroxidase or soybean peroxidase or, to a lesser degree, lactoperoxidase. This resulted in an increase in the cysticidal activity of 3% (wt/vol) H(2)O(2), and there was >3-log killing in 2 h, compared with the 6 h required for comparable results with the peroxide solution alone (P < 0.05). With 2% H(2)O(2), enhancement was observed at all time points (P < 0.05), and total killing of the cyst inoculum occurred at 4 h, compared with 6 h for the peroxide alone. The activity of sublethal 1% H(2)O(2) was enhanced to give 3-log killing after 8 h of exposure (P < 0.05). No enhancement was obtained when KCl or catalase was used as a substitute in the reaction mixtures. The H(2)O(2) was not neutralized in the enhanced system during the experiments. However, in the presence of a platinum disk used to neutralize H(2)O(2) in contact lens care systems, the enhanced 2% H(2)O(2) system gave 2.8-log killing after 6 h or total cyst killing by 8 h, and total neutralization of the H(2)O(2) occurred by 4 h. In contrast, 2% H(2)O(2) alone resulted in <0.8-log killing of cysts in the presence of the platinum disk due to rapid (<1 h) neutralization of the peroxide. Our observations could result in significant improvement in the efficacy of H(2)O(2) contact lens disinfection systems against Acanthamoeba cysts and prevention of acanthamoeba keratitis.
2000-02-25 | The increasing importance of Acanthamoeba infections.
Free-living amebae belonging to the genus Acanthamoeba are the causative agents of granulomatous amebic encephalitis, a chronic progressive disease of the central nervous system, and of amebic keratitis, a chronic eye infection. Granulomatous amebic encephalitis occurs more frequently in immunocompromised patients while keratitis occurs in healthy individuals. The recent increased incidence in Acanthamoeba infections is due in part to infection in patients with acquired immune deficiency syndrome, while that for keratitis is due to the increased use of contact lenses. Understanding the mechanism of host resistance to Acanthamoeba is essential since the amebae are resistant to many therapeutic agents. Studies in our laboratory as well as from others have demonstrated that macrophages from immunocompetent animals are important effector cells against Acanthamoeba. We have demonstrated also that microglial cells, resident macrophages of the brain, elicit cytokines in response to A. castellanii. Neonatal rat cortical microglia from Sprague-Dawley rats co-cultured with A. castellanii produced mRNA for the inflammatory cytokines, interleukin 1alpha, interleukin 1beta, and tumor necrosis factor alpha. In addition, scanning and transmission electron microscopy revealed that microglia ingested and destroyed A. castellanii in vitro. These results implicate macrophages as playing an effector role against Acanthamoeba and suggest immune modulation as a potential alternative therapeutic mode of treatment for these infections.
small molecules
2026-03-28 | Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence.
Devastating or nearly invariably fatal infections caused by free-living amoebae (FLA), including Acanthamoeba keratitis (AK), granulomatous amoebic encephalitis (GAE), and primary amoebic meningoencephalitis (PAM), remain a significant public health concern, driven by increasing case numbers, geographic expansion, and the lack of approved, effective, and safe treatments. Despite decades of research, no new drugs have been successfully approved, highlighting the severe limitations of de novo drug development for these infections, particularly for GAE and PAM, largely due to the challenges of conducting clinical trials for these rare and rapidly lethal diseases. In this context, drug repurposing represents a cost-effective and promising strategy to accelerate therapeutic advances and overcome key bottlenecks of conventional drug development. Accordingly, we conducted a systematic review of in vitro studies and animal models of AK, GAE, and PAM reported in indexed databases to identify promising drug repurposing candidates against FLA infections. After screening 23,624 records, 112 studies were included in the analysis. Overall, 2726 drugs and drug combinations, spanning 865 pharmacological classes and approved for 565 therapeutic indications, were assessed for their repurposing potential. Among these, 166 compounds showed substantial trophocidal activity (≥IC50) at potentially translatable concentrations (≤10 µM), including six with additional cysticidal activity. In vitro, four compounds were active against Balamuthia mandrillaris, 44 against Acanthamoeba spp. (three cysticidal), and 115 against Naegleria spp. (three cysticidal). In in vivo studies, sulfadiazine and rifampicin were effective as preventive or early monotherapies for GAE. For AK, the combination of polyhexamethylene biguanide, neomycin, and atropine, as well as voriconazole and nitazoxanide monotherapies, showed the greatest promise. In PAM, azithromycin alone or in combination with amphotericin B emerged as the most promising therapeutic options. Further studies are required to advance the clinical translatability of these findings. To the best of our knowledge, this work provides the first comprehensive and integrated synthesis of repurposable drug candidates against FLA infections.
2026-01-25 | Different roads to the brain: A brief overview of divergent pathways and convergent mechanisms in amoebic neuroinvasion.
Free-living amoebae such as Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri are opportunistic protists capable of causing devastating infections of the central nervous system. Although these organisms differ in ecology, morphology, and clinical progression, they converge on shared strategies that enable adhesion, immune evasion, and neuroinvasion. Here, we briefly present a comparative analysis of their routes of entry, molecular determinants, and neuropathogenic mechanisms with an eye to understand parallel and divergent pathways. A complete understanding of shared and distinct mechanisms can inform translational advances, including organoid-based modelling, multi-omics biomarker discovery, and therapeutic targeting of conserved host-pathogen signalling pathways.
2025-12-10 | Drug susceptibility of a clinical isolate of Balamuthia mandrillaris, a pathogenic free-living amoeba.
Balamuthia amoebic encephalitis (BAE) is a highly fatal infection caused by Balamuthia mandrillaris, an amoeba that lives in soil and water. In Thailand, three fatal cases of BAE have been documented, but no survivors have been reported, raising questions about current treatment regimens. Previous drug repurposing studies reveal some potent pharmacological compounds, but the drug susceptibility of the clinical isolate of pathogenic amoeba remains variable. Given the success in isolating B. mandrillaris from the human biopsied brain, this study aims to assess the amoebicidal effect of several previously repurposed drugs and suggested therapies for BAE. The trophozoites of a new clinical isolate, the KM-20 strain, were exposed to 12 compounds, including pentamidine, the most widely used antiprotozoal drug, and nitroxoline, the recent radical cure for BAE. The amoebicidal effect was assessed using the ATP level as a cell survival biomarker. The circularity and surface area of the cells were used as recrudescence indicators. Among all drugs tested, nitroxoline is the most potent amoebicidal drug without recrudescence. Topical antiseptic agents caused amoeba lysis at all doses tested, suggesting potential use for cutaneous balamuthiasis. Compared with two laboratory-adapted V039 and PRA-291 strains, the KM-20 isolate had reduced drug susceptibility to all of the tested compounds, suggesting strain dependency of amoebicidal activity. This study provides drug susceptibility data against a novel and geographically diverse clinical isolate of B. mandrillaris to assist in prioritizing anti-Balamuthia agents for further drug development testing, followed by in vivo efficacy testing animal models before clinical trials and drug repurposing.
2025-10-29 | A Review on Phytochemistry, Ethnopharmacology, and Antiparasitic Potential of Mangifera indica L.
Parasitic infections remain a major global health challenge, particularly in resource-limited settings where they are closely tied to poverty and inadequate sanitation. The increasing emergence of drug resistance and the limited accessibility of current therapies highlight the urgent need for novel, safe, and affordable alternatives. Mangifera indica L. (mango), a widely cultivated fruit tree deeply rooted in traditional medicine, has long been used to treat conditions symptomatic of parasitic diseases, including fever, diarrhea, and dysentery. Phytochemical investigations have revealed a rich spectrum of bioactive compounds, notably mangiferin, phenolic compounds and terpenoids, which exhibit antimicrobial, antioxidant, and immunomodulatory activities. This review critically synthesizes evidence on the antiparasitic potential of M. indica against protozoa, such as Plasmodium, Leishmania, Trypanosoma, Toxoplasma gondii, Entamoeba histolytica, and free-living amoebae, as well as helminths. Strongest evidence exists for malaria and helminth infections, where both crude extracts and isolated compounds demonstrated significant activity in vitro and in vivo. Encouraging but limited findings are available for leishmaniasis and trypanosomiasis, while data on toxoplasmosis and amoebiasis remain largely speculative. Variations in efficacy across studies are influenced by plant parts and extraction methods, with ethanolic extracts and mangiferin often showing superior results. Despite promising findings, mechanistic studies, standardized methodologies, toxicological evaluations, and clinical trials are scarce. Future research should focus on elucidating molecular mechanisms, exploring synergistic interactions with existing drugs, and leveraging advanced delivery systems to enhance bioavailability.
2025-09-05 | Ultrastructural characterization and pathogenicity of Allovohlkamfia spelaea in a murine model: Neuropulmonary infections and therapeutic potential of ellagic acid.
Allovahlkampfia spelaea (A. spelaea) is a free-living amoeba that has recently been recognized to cause Acanthamoeba-like keratitis, the treatment of which is complex. The pathogenic potential of Allovahlkampfia spp. remains unexplored. This study characterized A. spelaea through ultrastructural morphological analysis and investigated the pathogenic potential of the A. spelaea strain KS1, which was isolated from a patient with keratitis, in a murine model, with a focus on neuro-pulmonary infections. Additionally, this study assessed the therapeutic effectiveness of ellagic acid (EA) against tissue damage caused by amoebic infections. Immunosuppressed male Wister rats were intranasally inoculated with A. spelaea trophozoites (1 × 106/ml) and divided into control, infected untreated, and infected treated (50 mg/kg EA daily) groups. Histopathological and ultrastructural analyses of brain and lung tissues were conducted by scanning and transmission electron microscopy. Additionally, the therapeutic effects of EA were assessed via comparative tissue pathology. A. spelaea infection induced A. spelaea-induced neural lesions resembling granulomatous amoebic encephalitis (GAE) in the brain, which was characterized by gliosis, vasculitis, and necrosis, in addition to severe pulmonary damage, including suppurative bronchopneumonia and abscesses. Trophozoites presented with pseudopodia, acanthopodia, and amoebostomes, whereas cysts presented with double-layered walls. EA-treated rats presented nearly normal brain and lung histology, with reduced inflammation and gliosis, highlighting the anti-inflammatory and antioxidant properties of EA. This study highlights the neurotropic and pulmonary pathogenicity of A. spelaea, with ultrastructures parallel to those of Vahlkampfia spp. and Acanthamoeba spp. Ellagic acid significantly reduces infection-induced damage, underscoring its potential as a therapeutic agent for infections caused by free-living amoebae.
gene therapies
2024-10-03 | Comparative genomic analysis of Acanthamoeba from different sources and horizontal transfer events of antimicrobial resistance genes.
Acanthamoeba species are among the most common free-living amoeba and ubiquitous protozoa, mainly distributed in water and soil, and cause Acanthamoeba keratitis (AK) and severe visual impairment in patients. Although several studies have reported genomic characteristics of Acanthamoeba, limited sample sizes and sources have resulted in an incomplete understanding of the genetic diversity of Acanthamoeba from different sources. While endosymbionts exert a significant influence on the phenotypes of Acanthamoeba, including pathogenicity, virulence, and drug resistance, the species diversity and functional characterization remain largely unexplored. Herein, our study sequenced and analyzed the whole genomes of 19 Acanthamoeba pathogenic strains that cause AK, and by integrating publicly available genomes, we sampled 29 Acanthamoeba strains from ocular, environmental, and other sources. Combined pan-genomic and comparative functional analyses revealed genetic differences and evolutionary relationships among the different sources of Acanthamoeba, as well as classification into multiple functional groups, with ocular isolates in particular showing significant differences that may account for differences in pathogenicity. Phylogenetic and rhizome gene mosaic analyses of ocular Acanthamoeba strains suggested that genomic exchanges between Acanthamoeba and endosymbionts, particularly potential antimicrobial resistance genes trafficking including the adeF, amrA, and amrB genes exchange events, potentially contribute to Acanthamoeba drug resistance. In conclusion, this study elucidated the adaptation of Acanthamoeba to different ecological niches and the influence of gene exchange on the evolution of ocular Acanthamoeba genome, guiding the clinical diagnosis and treatment of AK and laying a theoretical groundwork for developing novel therapeutic approaches. Acanthamoeba causes a serious blinding keratopathy, Acanthamoeba keratitis, which is currently under-recognized by clinicians. In this study, we analyzed 48 strains of Acanthamoeba using a whole-genome approach, revealing differences in pathogenicity and function between strains of different origins. Horizontal transfer events of antimicrobial resistance genes can help provide guidance as potential biomarkers for the treatment of specific Acanthamoeba keratitis cases.
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Drug Discovery Landscape
4 orphan drug designations for Amoebiasis due to free-living amoebae.
4 orphan drug designations for Amoebiasis due to free-living amoebae.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
leucinostatin A | peptides | FDA | — | Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego |
miltefosine | small molecules | FDA | — | Profounda, Inc. |
miltefosine | small molecules | FDA | — | Profounda, Inc. |
corifungin | small molecules | FDA | — | Ctr for Discovery & Innovation in Parasitic Diseas |
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