ArticleAntimicrobial agents and chemotherapy2013
Small-molecule inhibitors of lethal factor protease activity protect against anthrax infection.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting virulence to disarm the pathogen: Enzyme-activated-substrate inhibition of Anthrax edema factor.Bioorganic & medicinal chemistry letters · 2025Article
- A comprehensive review on human disease-causing bacterial proteases and their impeding agents.Archives of microbiology · 2023Review
- Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome.Nature communications · 2020Article
- A multicomponent toxin from Bacillus cereus incites inflammation and shapes host outcome via the NLRP3 inflammasome.Nature microbiology · 2019Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
- Full Sequence Amino Acid Scanning of θ-Defensin RTD-1 Yields a Potent Anthrax Lethal Factor Protease Inhibitor.Journal of medicinal chemistry · 2017Article
- A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection.The Journal of biological chemistry · 2016Article
- Inhibiting bacterial toxins by channel blockage.Pathogens and disease · 2016Review
- Inhibitors of the Metalloproteinase Anthrax Lethal Factor.Current topics in medicinal chemistry · 2016Review
- Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.Antimicrobial agents and chemotherapy · 2015Article
- An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis.Expert opinion on investigational drugs · 2015Review
- Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.Biomacromolecules · 2014Article
- Anthrax lethal and edema toxins in anthrax pathogenesis.Trends in microbiology · 2014Review
- Designing inhibitors of anthrax toxin.Expert opinion on drug discovery · 2014Review
- Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin.Cell reports · 2013Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Bacillus anthracis, the causative agent of anthrax, manifests its pathogenesis through the action of two secreted toxins. The bipartite lethal and edema toxins, a combination of lethal factor or edema factor with the protein protective antigen, are important virulence factors for this bacterium. We previously developed small-molecule inhibitors of lethal factor proteolytic activity (LFIs) and demonstrated their in vivo efficacy in a rat lethal toxin challenge model. In this work, we show that these LFIs protect against lethality caused by anthrax infection in mice when combined with subprotective doses of either antibiotics or neutralizing monoclonal antibodies that target edema factor. Significantly, these inhibitors provided protection against lethal infection when administered as a monotherapy. As little as two doses (10 mg/kg) administered at 2 h and 8 h after spore infection was sufficient to provide a significant survival benefit in infected mice. Administration of LFIs early in the infection was found to inhibit dissemination of vegetative bacteria to the organs in the first 32 h following infection. In addition, neutralizing antibodies against edema factor also inhibited bacterial dissemination with similar efficacy. Together, our findings confirm the important roles that both anthrax toxins play in establishing anthrax infection and demonstrate the potential for small-molecule therapeutics targeting these proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.