Mechanisms of quinolone resistance in Salmonella

Abstract

-As in other Gram-negative bacteria, mechanisms of resistance to quinolones in Salmonella include target gene mutations, active efflux, and decreased outer membrane permeability. However, the exact contribution of these individual mechanisms to resistance, which may nevertheless interplay to reach high-level resistance, has not yet clearly been defined as in other bacteria such as Escherichia coli. This paper reviews the current state of knowledge of quinolone resistance mechanisms in Salmonella by comparison with that of E. coli and future directions of research with particular attention to the recent development of efflux pump inhibitors as possible means of avoiding the emergence and spread of fluoroquinolone resistance.Salmonella / quinolone / resistance / mechanism Résumé -Mécanismes de résistance aux quinolones chez Salmonella. Comme chez les autres bactéries Gram-négatives les mécanismes de résistance aux quinolones chez Salmonella comprennent les mutations dans les gènes cibles, l'efflux actif, et une diminution de la perméabilité de la membrane externe. Cependant la contribution exacte de ces mécanismes individuels, qui peuvent néanmoins interagir pour atteindre des niveaux de résistance élevés, n'a pas encore été clairement définie comme chez d'autres bactéries telle que Escherichia coli. Cette revue présente l'état actuel des connaissances des mécanismes de résistance chez Salmonella par comparaison avec E. coli et des perspectives futures de recherche avec une attention particulière au développement récent d'inhibiteurs de pompes d'efflux comme moyen possible pour éviter l'émergence et la diffusion de la résistance aux fluoroquinolones.Salmonella / quinolone / résistance / mécanisme Vet. Res. 32 (2001) 291-300 291

Emergence of Salmonella epidemics: The problems related to Salmonella enterica serotyp Enteritidis and multiple antibiotic resistance in other major serotypes

“…Resistance mutations of gyrA occur in a region of the gene product between amino acids 67 and 106, termed the quinolone resistance-determining region (QRDR). Amino acid changes at Ser-83 (to Phe, Tyr, or Ala) or at Asp-87 (to Gly, Asn, or Tyr) are the most frequently observed in nalidixic acid (Nal)-resistant strains [30]. Double mutations at both residues 83 and 87 have been identified in clinical isolates of an S. Typhimurium DT204 clone showing high-level resistance to FQ [67].…”

Use of antimicrobials in veterinary medicine and mechanisms of resistance

“…Enzymatic inactivation has not been observed so far. The molecular basis and epidemiology of quinolone resistance in E. coli and Salmonella was reviewed by Cloeckaert and Chaslus-Dancla [16], Webber and Piddock [73] and Bager and Helmuth [4], respectively.…”

“…A wide variety of mutations has been detected in the various target genes of a wide range of gram-positive and gram-negative bacteria of human and veterinary importance [16,23,27]. The effect of the different mutations on resistance also differs with respect to the various fluoroquinolones [30].…”

“…aeruginosa (MexAB/OprM, MexCD/OprJ), S. aureus (NorA), S. pneumoniae (PmrA), B. subtilis (Blt), E. coli and Salmonella (AcrAB/TolC). For reviews, see references [16,[45][46][47]. Many of these efflux systems represent multidrug transporters which are able to export, in addition to quinolones, a wide range of other toxic substances from the bacterial cell [16,[44][45][46].…”

“…For reviews, see references [16,[45][46][47]. Many of these efflux systems represent multidrug transporters which are able to export, in addition to quinolones, a wide range of other toxic substances from the bacterial cell [16,[44][45][46]. Since the basal level of expression of these efflux systems is low, upregulation of their expression is required to confer resistance to fluoroquinolones and other antimicrobials.…”