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Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India.
J Antimicrob Chemother. 2006 Dec; 58(6):1139-44.JA

Abstract

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-83-->Tyr) was associated with reduced susceptibility to ciprofloxacin (MICs 0.125-1 mg/L); an additional mutation in parC (Ser-80-->Ile, Ser-80-->Arg, Asp-69-->Glu or Gly-78-->Asp) was accompanied by an increase in ciprofloxacin MIC (> or = 0.5 mg/L). Three mutations conferred ciprofloxacin resistance: two in gyrA (Ser-83-->Phe and Asp-87-->Asn or Asp-87-->Gly) 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.

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Authors+Show Affiliations

Gaind R
Department of Microbiology, Safdarjung Hospital and Assoc VMMC, New Delhi, India.
Paglietti B
No affiliation info available
Murgia M
No affiliation info available
Dawar R
No affiliation info available
Uzzau S
No affiliation info available
Cappuccinelli P
No affiliation info available
Deb M
No affiliation info available
Aggarwal P
No affiliation info available
Rubino S
No affiliation info available

MeSH

Amino Acid SubstitutionAnti-Bacterial AgentsCiprofloxacinDNA GyraseDNA Topoisomerase IVDNA TopoisomerasesDNA, BacterialDeoxyribonucleases, Type II Site-SpecificDrug Resistance, BacterialElectrophoresis, Gel, Pulsed-FieldHumansIndiaIntegronsMicrobial Sensitivity TestsMutation, MissenseParatyphoid FeverPlasmidsSalmonella paratyphi ASalmonella typhiSequence Analysis, DNATetracyclineTrimethoprim, Sulfamethoxazole Drug CombinationTyphoid Fever

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17071955

Citation

Gaind, R, et al. "Molecular Characterization of Ciprofloxacin-resistant Salmonella Enterica Serovar Typhi and Paratyphi a Causing Enteric Fever in India." The Journal of Antimicrobial Chemotherapy, vol. 58, no. 6, 2006, pp. 1139-44.
Gaind R, Paglietti B, Murgia M, et al. Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India. J Antimicrob Chemother. 2006;58(6):1139-44.
Gaind, R., Paglietti, B., Murgia, M., Dawar, R., Uzzau, S., Cappuccinelli, P., Deb, M., Aggarwal, P., & Rubino, S. (2006). Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India. The Journal of Antimicrobial Chemotherapy, 58(6), 1139-44.
Gaind R, et al. Molecular Characterization of Ciprofloxacin-resistant Salmonella Enterica Serovar Typhi and Paratyphi a Causing Enteric Fever in India. J Antimicrob Chemother. 2006;58(6):1139-44. PubMed PMID: 17071955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India. AU - Gaind,R, AU - Paglietti,B, AU - Murgia,M, AU - Dawar,R, AU - Uzzau,S, AU - Cappuccinelli,P, AU - Deb,M, AU - Aggarwal,P, AU - Rubino,S, Y1 - 2006/10/28/ PY - 2006/10/31/pubmed PY - 2007/3/23/medline PY - 2006/10/31/entrez SP - 1139 EP - 44 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 58 IS - 6 N2 - 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-83-->Tyr) was associated with reduced susceptibility to ciprofloxacin (MICs 0.125-1 mg/L); an additional mutation in parC (Ser-80-->Ile, Ser-80-->Arg, Asp-69-->Glu or Gly-78-->Asp) was accompanied by an increase in ciprofloxacin MIC (> or = 0.5 mg/L). Three mutations conferred ciprofloxacin resistance: two in gyrA (Ser-83-->Phe and Asp-87-->Asn or Asp-87-->Gly) 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. SN - 0305-7453 UR - https://www.unboundmedicine.com/medline/citation/17071955/Molecular_characterization_of_ciprofloxacin_resistant_Salmonella_enterica_serovar_Typhi_and_Paratyphi_A_causing_enteric_fever_in_India_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkl391 DB - PRIME DP - Unbound Medicine ER -