A clinical drug library screen identifies tosufloxacin as being highly active against staphylococcus aureus persisters

Hongxia Niu, Peng Cui, Rebecca Yee, Wanliang Shi, Shuo Zhang, Jie Feng, David Sullivan, Wenhong Zhang, Bingdong Zhu, Ying Zhang

Research output: Contribution to journalArticle

Abstract

To identify effective compounds that are active against Staphylococcus aureus (S. aureus) persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalAntibiotics
Volume4
Issue number3
DOIs
StatePublished - Jul 31 2015

Keywords

  • Clinafloxacin
  • Clinical drug library
  • Persisters
  • Staphylococcus aureus
  • Tosufloxacin

ASJC Scopus subject areas

  • Microbiology
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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