JAC Advance Access originally published online on October 28, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1139-1144; doi:10.1093/jac/dkl391
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Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India
1 Department of Microbiology, Safdarjung Hospital and Assoc VMMC New Delhi, India 2 Department of Biomedical Sciences, Division of Experimental and Clinical Microbiology, University of Sassari, Sassari Italy
Received 7 April 2006; returned 26 July 2006; revised 20 August 2006; accepted 6 September 2006
*Corresponding author. Tel: +39-79-228302; Fax: +39-79-212345; E-mail: rubino{at}uniss.it
Objectives: To define the genetic characteristics and resistance mechanisms of clinical isolates of Salmonella enterica serovar Typhi (S. Typhi) and S. enterica serovar Paratyphi A (S. Paratyphi A) exhibiting high-level fluoroquinolones resistance.
Methods: Three S. Typhi and two S. Paratyphi A ciprofloxacin-resistant isolates (MICs > 4 mg/L) were compared with isolates with reduced susceptibility to ciprofloxacin (MICs 0.125–1 mg/L) by PFGE, plasmid analysis, presence of integrons and nucleotide changes in topoisomerase genes.
Results: In S. Typhi and Paratyphi A, a single gyrA mutation (Ser-83
Phe or Ser-83Tyr) was associated with reduced susceptibility to ciprofloxacin (MICs 0.125–1 mg/L); an additional mutation in parC (Ser-80Ile, Ser-80Arg, Asp-69Glu or Gly-78Asp) was accompanied by an increase in ciprofloxacin MIC (
0.5 mg/L). Three mutations conferred ciprofloxacin resistance: two in gyrA (Ser-83Phe and Asp-87Asn or Asp-87Gly) and one in parC. This is the first report of parC mutations in S. Typhi. Ciprofloxacin-resistant S. Typhi and S. Paratyphi A differed in their MICs and mutations in gyrA and parC. Moreover S. Typhi harboured a 50 kb transferable plasmid carrying a class 1 integron (dfrA15/aadA1) that confers resistance to co-trimoxazole and tetracycline but not to ciprofloxacin. PFGE revealed undistinguishable XbaI fragment patterns in ciprofloxacin-resistant S. Typhi as well as in S. Paratyphi A isolates and showed that ciprofloxacin-resistant S. Typhi have emerged from a clonally related isolate with reduced susceptibility to ciprofloxacin after sequential acquisition of a second mutation in gyrA.
Conclusions: To our knowledge this is the first report of molecular characterization of S. Typhi with full resistance to ciprofloxacin. Notably, the presence of a plasmid-borne integron in ciprofloxacin-resistant S. Typhi may lead to a situation of untreatable enteric fever.
Keywords: Salmonella enterica serovar Paratyphi A , DNA gyrase , topoisomerase IV , integrons , high-level fluoroquinolone resistance
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