A deletion mutation in nfxB of in vitro-induced moxifloxacin-resistant Pseudomonas aeruginosa confers multidrug resistance

Acta Microbiol Immunol Hung. 2017 Sep 1;64(3):245-253. doi: 10.1556/030.64.2017.012. Epub 2017 May 31.

Abstract

The modulation of efflux pump functions under fluoroquinolone (FQ) exposure is of great concern as it could result in occurrence of multidrug-resistant (MDR) bacterial strains. In this study, MDR mechanism in Pseudomonas aeruginosa induced via moxifloxacin (MOX) pressure was investigated. After serial MOX [concentration of 0.5 × the minimum inhibitory concentration (MIC)] exposure, the fully susceptible P. aeruginosa ATCC 9027 strain has increased its MIC not only toward MOX (1→128 mg/L) but also to other antibiotics. Furthermore, this MOX-exposed strain did not revert to antibiotic-sensitive phenotype when being cultured in antibiotic-free medium for 12 days. No mutation was observed for FQ-target (gyrA and parC) or most investigated efflux regulatory genes (mexT, mexR, and nalC) except nfxB in which a 100-bp deletion was found. This associated with the elevated expression of multidrug efflux pump operon (mexCD-oprJ) which could directly result in MDR phenotype.

Keywords: P. aeruginosa; moxifloxacin; multidrug resistance; nfxB.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Fluoroquinolones / pharmacology*
  • Gene Deletion
  • Gene Expression Regulation, Bacterial / physiology
  • Moxifloxacin
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Fluoroquinolones
  • NfxB protein, Pseudomonas aeruginosa
  • Transcription Factors
  • Moxifloxacin