2026-07-17 | In vitro activity and in vivo efficacy of sulopenem against Bacillus anthracis in inhalational anthrax mouse and rabbit models.
Bacillus anthracis is a gram-positive, spore-forming bacterium and the etiological agent of anthrax. As a Tier 1 Select Agent, the pathogen can be isolated from the natural environment, and the endospore is a significant biological threat that can be produced in large quantities, stored, and disseminated by aerosolization. The intentional release of B. anthracis spores has the potential for mass casualties and is a serious threat to public and military health. Fluoroquinolones and tetracyclines are common antibiotics used for post-exposure prophylaxis and treatment in the United States (U.S.), whereas penicillin is the drug of choice throughout the rest of the world. However, these commonly used antibiotics may be contraindicated or suboptimal in a public health crisis. Thus, there is a need for novel medical countermeasures to be developed and tested against B. anthracis. Sulopenem is a broad-spectrum, orally bioavailable penem antibiotic recently approved in the U.S. for the treatment of uncomplicated urinary tract infections in women with limited therapeutic options. Here, we demonstrate that sulopenem has potent in vitro activity against both wild-type virulent B. anthracis strains, as well as biosafety level 2 surrogate strains resistant to current standards of care. Using human-equivalent dosing regimens, we show that sulopenem is highly protective in both the mouse and rabbit inhalational anthrax models. Together, these results support continued evaluation of this oral penem as a countermeasure for inhalational anthrax.
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2026-05-21 | Cough
This case describes a patient who comes in with cough and shortness of breath. The course of inhalational anthrax can progress from initial nonspecific viral symptoms to severe respiratory distress, hypotension, hypoxia, tachypnea, cyanosis, and hemorrhage within days. Pathognomonic imaging findings include mediastinal widening due to hemorrhagic mediastinitis, pleural effusion, and mediastinal lymphadenopathy.
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2026-04-20 | Cytosol-Targeting Delivery of Non-Nucleotide STING Agonist Achieves Inhalable Nanoparticle-Based Anthrax Vaccine.
Inhalational anthrax is a deadly disease caused by inhalation of Bacillus anthracis spores. Current anthrax vaccines for human use have limitations including undefined components, limited mucosal immunity, and suboptimal adjuvant delivery. This study introduces 2 polymers, MP1 and MP2, each containing disulfide bonds. MP1 incorporates tertiary amines to induce proton sponge effect, while MP2 features terminal phenylboronic acid moieties for protein conjugation. Nanoparticle vaccine YM1.7 is created through self-assembly of MP1, MP2, and STING agonist MSA-2, followed by N─B coordination of recombinant protein antigen (rPA) on its surface. When administered via aerosolized intratracheal inoculation into the lung, YM1.7 is internalized by antigen-presenting cell and trafficked to the lysosome, where acidic environment dissociates N─B bond, releasing rPA for antigen presentation. Proton sponge effect allows nanoparticle to escape into the cytosol, and then disulfide bond cleavage triggered by cytosolic glutathione causes dissociation of nanoparticle and release of MSA-2 within the cytosol, significantly enhancing bioavailability of MSA-2 as an adjuvant. This spatiotemporal delivery mechanism elicits a coordinated innate, humoral, mucosal, and cell-mediated immune response in mice, providing strong protection against inhalational anthrax. Given its modular design nature, YM1.7 represents a promising platform for developing next-generation mucosal vaccines against infections and cancers.
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2026-02-12 | Enhancing bioinformatics engineering by utilizing graph therapeutic properties for clinically approved antitoxin drugs in zoonotic diseases
Anthrax, a zoonotic disease caused by the bacterium Bacillus anthracis. It primarily affects animals and spreads to humans through direct contact or inhalation. This article examines the correlations between physicochemical properties and topological indices of the chemical structures of drugs used to mitigate anthrax disease. This study considers the clinically approved drugs, including ciprofloxacin, levaquin, doryx, penicillin tetrapropyl, and pfizerpen, etc. For the chemical structures of these drugs, we have calculated M-polynomials of various reverse topological indices, including the reverse Zagreb-type indices, reverse atom-bond connectivity index, reverse harmonic index, and reverse sum connectivity index, etc. The relationships identified through regression analysis establish quantitative structure-property relationships (QSPR), offering insights into how the molecular structure governs the physical behavior of these antitoxins, which is foundational for future drug optimization efforts. Our findings highlight the regression coefficients that achieved the lowest SE and the maximum $$R^2$$ values, indicating the strongest structure-property correlations (such as for Molecular Weight). These robust coefficients can be used to model the structural properties of chemically similar compounds.
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2026-01-01 | P-1180. Effects of a Novel Bacterial Topoisomerase Inhibitor on Type II Topoisomerases in Bacillus anthracis
Abstract Background The tier 1 agent, Bacillus anthracis (etiological cause of anthrax) is a highly transmissible pathogen that causes morbidity and mortality. The intentional release of anthrax spores from either wild-type or drug-resistant strains would constitute a severe threat to public and military health. Novel Bacterial Topoisomerase Inhibitors (NBTIs) are emerging antibacterials that target the type II topoisomerases, gyrase and topoisomerase IV. The NBTI pharmacophore promotes a binding mode that allows for the evasion of target-mediated fluoroquinolone (FQ) resistance. OSUAB0284 is a pre-clinical NBTI candidate that shows potent anti-staphylococcal activity in cultured cells and a neutropenic mouse model.1,2 Gepotidacin is an advanced NBTI-type first-in-class triazaacenapthylene. It has completed phase III clinical trials for the treatment of uncomplicated urogenital gonorrhea with positive outcomes and was approved by the FDA for the treatment of uncomplicated urinary tract infections.3-5Antimicrobial AgentsThe compounds analyzed in this work: ciprofloxacin (FQ), gepotidacin (triazaacenaphthylene), OSUAB0284 (NBTI) Methods Beyond its clinical success, gepotidacin displayed potent activity against wild-type and FQ-resistant strains of B. anthracis in vitro and in vivo.6 Consequently, we analyzed the effects of OSUAB0284 in parallel to ciprofloxacin (an FQ) and gepotidacin in cell- and enzyme-based B. anthracis experiments. Results Ciprofloxacin, gepotidacin, and OSUAB0284 displayed potent antibacterial activity against cultured B. anthracis (MIC90 = 0.06 µg/mL, 0.5 µg/mL, and 0.25 µg/mL, respectively). OSUAB0284 and gepotidacin induced high levels of single-stranded DNA cleavage mediated by purified wild-type B. anthracis gyrase and topoisomerase IV, a mechanism distinct from FQs. DNA cleavage activity was maintained against FQ-resistant gyrase enzymes (GyrAS85L and GyrAE89K). OSUAB0284 and gepotidacin induced even higher levels of DNA cleavage with FQ-resistant topoisomerase IV enzymes (ParCS81Y and ParCE85K) compared to wild-type. OSUAB0284 and gepotidacin inhibited the catalytic function of wild-type B. anthracis gyrase and topoisomerase IV and maintained activity with the FQ-resistant enzymes. Conclusion An inhalation anthrax model in mice treated with OSUAB0284 is ongoing. Our results suggest that NBTIs are potential therapeutic candidates for use against B. anthracis. Disclosures Mark Mitton-Fry, PhD, Pfizer: Stocks/Bonds (Public Company)|Viatris: Stocks/Bonds (Public Company)
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