Differential Gene Expression by RamA in Ciprofloxacin-Resistant Salmonella Typhimurium

PLoS One. 2011;6(7):e22161. doi: 10.1371/journal.pone.0022161. Epub 2011 Jul 19.

Abstract

Overexpression of ramA has been implicated in resistance to multiple drugs in several enterobacterial pathogens. In the present study, Salmonella Typhimurium strain LTL with constitutive expression of ramA was compared to its ramA-deletion mutant by employing both DNA microarrays and phenotype microarrays (PM). The mutant strain with the disruption of ramA showed differential expression of at least 33 genes involved in 11 functional groups. The study confirmed at the transcriptional level that the constitutive expression of ramA was directly associated with increased expression of multidrug efflux pump AcrAB-TolC and decreased expression of porin protein OmpF, thereby conferring multiple drug resistance phenotype. Compared to the parent strain constitutively expressing ramA, the ramA mutant had increased susceptibility to over 70 antimicrobials and toxic compounds. The PM analysis also uncovered that the ramA mutant was better in utilization of 10 carbon sources and 5 phosphorus sources. This study suggested that the constitutive expression of ramA locus regulate not only multidrug efflux pump and accessory genes but also genes involved in carbon metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Carbon / pharmacology
  • Ciprofloxacin / pharmacology*
  • Drug Resistance, Bacterial / drug effects
  • Drug Resistance, Bacterial / genetics*
  • Gene Deletion
  • Gene Expression Profiling*
  • Gene Expression Regulation, Bacterial / drug effects*
  • Genes, Bacterial / genetics
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphates / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism

Substances

  • Anti-Infective Agents
  • Bacterial Proteins
  • Multidrug Resistance-Associated Proteins
  • Phosphates
  • RNA, Messenger
  • RamA protein, Salmonella typhimurium
  • Trans-Activators
  • Ciprofloxacin
  • Carbon