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Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella Enterica Serotype Enteritidis: Reduced Infectivity Associated With Decreased Expression of Salmonella Pathogenicity Island 1 Genes

Fitness Costs and Stability of a High-Level Ciprofloxacin Resistance Phenotype in Salmonella Enterica Serotype Enteritidis: Reduced Infectivity Associated With Decreased Expression of Salmonella Pathogenicity Island 1 Genes

Edel O'Regan, Teresa Quinn, Jonathan G Frye, Jean-Marie Pagès, Steffen Porwollik, Paula J Fedorka-Cray, Michael McClelland, Séamus Fanning

Antimicrob Agents Chemother. 2010 Jan;54(1):367-74.

PMID: 19917752

Abstract:

The fitness costs associated with high-level fluoroquinolone resistance were examined for phenotypically and genotypically characterized ciprofloxacin-resistant Salmonella enterica serotype Enteritidis mutants (104-cip and 5408-cip; MIC, >32 microg/ml). The stability of the fluoroquinolone resistance phenotype in both mutants was investigated to assess whether clones with better fitness could emerge in the absence of antibiotic selective pressure. Mutants 104-cip and 5408-cip displayed altered morphology on agar and by electron microscopy, reduced growth rates, motility and invasiveness in Caco-2 cells, and increased sensitivity to environmental stresses. Microarray data revealed decreased expression of virulence and motility genes in both mutants. Two clones, 104-revert and 1A-revertC2, with ciprofloxacin MICs of 3 and 2 microg/ml, respectively, were recovered from separate lineages of 104-cip after 20 and 70 passages, respectively, on antibiotic-free agar. All fitness costs, except motility, were reversed in 104-revert. Potential mechanisms associated with reversal of the resistance phenotype were examined. Compared to 104-cip, both 104-revert and 1A-revertC2 showed decreased expression of acrB and soxS but still overexpressed marA. Both acquired additional mutations in SoxR and ParC, and 1A-revertC2 acquired two mutations in MarA. The altered porin and lipopolysaccharide (LPS) profiles observed in 104-cip were reversed. In contrast, 5408-cip showed no reversal in fitness costs and maintained its high-level ciprofloxacin resistance for 200 passages on antibiotic-free agar. In conclusion, high-level ciprofloxacin resistance in S. Enteritidis is associated with fitness costs. In the absence of antibiotic selection pressure, isolates may acquire mutations enabling reversion to an intermediate-level ciprofloxacin resistance phenotype associated with less significant fitness costs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS741386	Lipopolysaccharides from Salmonella enterica serotype enteritidis			Price

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