Evaluating new compounds to treat Burkholderia pseudomallei infections

Brittany N. Ross, Julia N. Myers, Laura A. Muruato, Daniel Tapia, Alfredo Torres

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Burkholderia pseudomallei is the causative agent of melioidosis, a disease that requires long-term treatment regimens with no assurance of bacterial clearance. Clinical isolates are intrinsically resistant to most antibiotics and in recent years, isolates have been collected that display resistance to frontline drugs. With the expanding global burden of B. pseudomallei, there is a need to identify new compounds or improve current treatments to reduce risk of relapse. Using the Pathogen Box generated by Medicines for Malaria Venture, we screened a library of 400 compounds for bacteriostatic or bactericidal activity against B. pseudomallei K96243 and identified seven compounds that exhibited inhibitory effects. New compounds found to have function against B. pseudomallei were auranofin, rifampicin, miltefosine, MMV688179, and MMV688271. An additional two compounds currently used to treat melioidosis, doxycycline and levofloxacin, were also identified in the screen. We determined that the minimal inhibitory concentrations (MIC) for levofloxacin, doxycycline, and MMV688271 were below 12 μg/ml for 5 strains of B. pseudomallei. To assess persister frequency, bacteria were exposed to 100x MIC of each compound. Auranofin, MMV688179, and MMV688271 reduced the bacterial population to an average of 4.53 × 10-6% compared to ceftazidime, which corresponds to 25.1% survival. Overall, our data demonstrates that auranofin, MMV688197, and MMV688271 have the potential to become repurposed drugs for treating melioidosis infections and the first evidence that alternative therapeutics can reduce B. pseudomallei persistence.

Original languageEnglish (US)
Article number210
JournalFrontiers in cellular and infection microbiology
Volume8
Issue numberJUN
DOIs
StatePublished - Jun 25 2018

Fingerprint

Burkholderia Infections
Burkholderia pseudomallei
Auranofin
Melioidosis
Levofloxacin
miltefosine
Doxycycline
Drug Repositioning
Ceftazidime
Rifampin
Malaria
Anti-Bacterial Agents
Bacteria
Recurrence
Infection

Keywords

  • Antibiotic resistance
  • Burkholderia
  • Pathogen box
  • Persistence
  • Treatment

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Evaluating new compounds to treat Burkholderia pseudomallei infections. / Ross, Brittany N.; Myers, Julia N.; Muruato, Laura A.; Tapia, Daniel; Torres, Alfredo.

In: Frontiers in cellular and infection microbiology, Vol. 8, No. JUN, 210, 25.06.2018.

Research output: Contribution to journalArticle

Ross, Brittany N. ; Myers, Julia N. ; Muruato, Laura A. ; Tapia, Daniel ; Torres, Alfredo. / Evaluating new compounds to treat Burkholderia pseudomallei infections. In: Frontiers in cellular and infection microbiology. 2018 ; Vol. 8, No. JUN.
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