Repurposing screens identify rifamycins as potential broad-spectrum therapy for multidrug-resistant Acinetobacter baumannii and select agent microorganisms

Brett A. Chromy, Maher Elsheikh, Tova L. Christensen, Doug Livingston, Kyle Petersen, Jane P. Bearinger, Paul D. Hoeprich

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Aims: Estimates suggest that the drug discovery and development processes take between 10 and 15 years, with costs ranging between US$500 million and $2 billion. A growing number of bacteria have become resistant to approved antimicrobials. For example, the Gram-negative bacterium Acinetobacter baumannii has become multidrug resistant (MDR) and is now an important pathogen to the US military in terms of wound infections. Industry experts have called for a 'disruptive transformation of the drug discovery process to find new chemical entities for treating drug-resistant infections. One such attempt is drug 'repurposing or 'repositioning - that is, identification and development of new uses for existing or abandoned pharmacotherapies. Materials & methods: Using a novel combination of screening technologies based on cell growth and cellular respiration, we screened 450 US FDA-approved drugs from the NIH National Clinical Collection against a dozen clinical MDR A. baumannii (MDRAb) isolates from US soldiers and Marines. We also screened the collection against a diverse set of select agent surrogate pathogens. Results: Seventeen drugs showed promising antimicrobial activity against all MDRAb isolates and select agent surrogates; three of these compounds - all rifamycins - were found to be effective at preventing growth and preventing cellular respiration of MDRAb and select agent surrogate bacteria when evaluated in growth prevention assays, highlighting the potential for repurposing. Conclusion: We report the discovery of a class of known compounds whose repurposing may be useful in solving the current problem with MDRAb and may lead to the discovery of broad-spectrum antimicrobials.

Original languageEnglish (US)
Pages (from-to)1011-1020
Number of pages10
JournalFuture Microbiology
Volume7
Issue number8
DOIs
StatePublished - Aug 2012

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Keywords

  • Acinetobacter baumannii
  • Bacillus anthracis
  • Francisella tularensis
  • rifamycins
  • select agent pathogens
  • Yersinia pestis

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Chromy, B. A., Elsheikh, M., Christensen, T. L., Livingston, D., Petersen, K., Bearinger, J. P., & Hoeprich, P. D. (2012). Repurposing screens identify rifamycins as potential broad-spectrum therapy for multidrug-resistant Acinetobacter baumannii and select agent microorganisms. Future Microbiology, 7(8), 1011-1020. https://doi.org/10.2217/fmb.12.75