title: Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica.
abstract: OBJECTIVE
  To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates.
  
  
  METHODS
  Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated.
  
  
  RESULTS
  Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F). Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC.
  
  
  CONCLUSIONS
  Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gram-negative clinical isolates.
authors.affiliation: College of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt. abeerahmedr@gmail.com
authors.forename: Abeer Ahmed
authors.initials: AA
authors.lastname: Rushdy
authors.forename: Mona Ibrahim
authors.initials: MI
authors.lastname: Mabrouk
authors.forename: Ferialla Abdel-Hamid
authors.initials: FA
authors.lastname: Abu-Sef
authors.forename: Zeinab Hassan
authors.initials: ZH
authors.lastname: Kheiralla
authors.forename: Said
authors.initials: S
authors.lastname: Mohamed Abdel-All
authors.forename: Neveen Mohamed
authors.initials: NM
authors.lastname: Saleh
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
keywords: Chromosomal mutations; Efflux pump; Fluoroquinolone resistance; Outer membrane protein; Salmonella