An in situ high-throughput screen identifies inhibitors of intracellular Burkholderia pseudomallei with therapeutic efficacy
Abstract
Burkholderia pseudomallei , the etiologic agent of melioidosis, is an environmental organism that inhabits tropical soils and kills an estimated 90,000 people each year. Caused by an intracellular and often drug-resistant pathogen, melioidosis is notoriously difficult to treat, with mortality rates approaching 50% in some settings despite appropriate diagnosis and clinical management. Using a high-throughput, cell-based phenotypic screen we have discovered 2 antibiotic candidates with improved in vivo efficacy compared to the current standard of care: a fluoroquinolone analog, burkfloxacin, and an FDA-approved antifungal drug, flucytosine. As a widely used antifungal with a well-known safety profile, the potential to repurpose flucytosine for treating melioidosis may represent a rapid route to clinical translation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 22, 2019
- Source ID
- 10.1073/pnas.1906388116
Entities
People
- Apichai Tuanyok
- Babak Toffig
- Bryan France
- Christopher T. French
- Herbert P Schweizer
- Isabelle J. Toesca
- Jeff F. Miller
- Jeffrey P. Maloy
- Marco Morselli
- Matteo Pellegrini
- Michael H Norris
- Nawarat Somprasong
- Philip L. Bulterys
- Robert Damoiseaux
- Sorel T Fitz-Gibbon
Organizations
- Defense Threat Reduction Agency
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- University of California
- University of California, Los Angeles
- University of Florida