title: Correlation of the expression of acrB and the regulatory genes marA, soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York City.
abstract: OBJECTIVE
  Nosocomial isolates of Klebsiella pneumoniae resistant to all commonly used antimicrobial agents have emerged in many regions of the world. It is unknown if efflux systems contribute to the multidrug resistance phenotype.
  
  
  METHODS
  The expression of genes encoding the efflux pump AcrAB and the global regulators MarA, SoxS and RamA were examined and correlated with antimicrobial resistance.
  
  
  RESULTS
  Twenty isolates belonged to the two important clones representing KPC-possessing strains endemic to our region. Virtually all of these isolates had negligible or absent expression of the genes, and resistance to fluoroquinolones and aminoglycosides could be explained by alternative mechanisms. All of these isolates were susceptible to tigecycline. A group of 14 heterogeneous isolates was also examined. There was a correlation between expression of marA with expression of soxS. Only expression of soxS was significantly correlated with expression of acrB. With a background substitution in GyrA, increased expression of acrB and marA appeared to contribute to fluoroquinolone resistance in some isolates. A correlation was noted between expression of soxS and ramA (but not marA and acrB) and tigecycline MICs. Following in vitro exposure to tigecycline, resistance occurred in association with a marked increase in marA and acrB expression in isolates lacking expression of soxS and ramA.
  
  
  CONCLUSIONS
  While laboratory-derived tigecycline resistance was associated with increased acrB expression, the variation in tigecycline MICs in clinical isolates was associated only with selected regulator genes. It appears that other mechanisms beyond activation of the acrAB system mediate tigecycline resistance.
authors.affiliation: Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Bratu
authors.forename: David
authors.initials: D
authors.lastname: Landman
authors.forename: Avrille
authors.initials: A
authors.lastname: George
authors.forename: Jerome
authors.initials: J
authors.lastname: Salvani
authors.forename: John
authors.initials: J
authors.lastname: Quale
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D024881:Drug Resistance, Bacterial; D019353:Endemic Diseases; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009519:New York City / Q000453:epidemiology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C095947:RamA protein, Klebsiella; D000078304:Tigecycline; D008911:Minocycline