Modulation of Salmonella gene expression by subinhibitory concentrations of quinolones

J Antibiot (Tokyo). 2011 Jan;64(1):73-8. doi: 10.1038/ja.2010.137. Epub 2010 Nov 24.

Abstract

Approximately 2.7% of a collection of Salmonella enterica var. Typhimurium promoter-lux reporter strains showed altered transcriptional patterns when exposed to low concentrations of nine different fluoroquinolones (FQs). Even at the subinhibitory concentrations employed, all nine FQs upregulated genes involved in the SOS response, umuD, lexA, sbmC and dinP. In addition, transcriptional regulators, genes putatively associated with membrane integrity (spr), virulence (sicA) and metabolism (plsB) were affected. Using the Ames test with Salmonella strain TA102, increased mutagenicity was demonstrated in response to all the FQs tested: ciprofloxacin, moxifloxacin, levofloxacin and gatifloxacin. Transcriptional effects were largely specific to the FQ antimicrobials. Such responses are consistent with the primary mechanism of action of this class of inhibitor, namely, the introduction of DNA damage. This work provides support for the notion that small molecules can have functions other than growth inhibition that may affect the establishment and maintenance of community dynamics in complex environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Fluoroquinolones / pharmacology*
  • Gene Expression Regulation, Bacterial / drug effects*
  • Microbial Sensitivity Tests
  • Mutagenicity Tests
  • SOS Response, Genetics / drug effects
  • SOS Response, Genetics / genetics
  • Salmonella Infections / drug therapy
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*

Substances

  • Anti-Infective Agents
  • Fluoroquinolones