Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India
Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India
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DOI：
10.1093/jac/dkl391
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发表时间：
2006-12-01
影响因子：
5.2
通讯作者：
Rubino, S.
中科院分区：
文献类型：
--
作者：
Gaind, R.;Paglietti, B.;Rubino, S.
目的：明确伤寒沙门氏菌和甲型副伤寒沙门氏菌临床分离株对氟喹诺酮类药物高度耐药的遗传特征和耐药机制。方法：对3株伤寒沙门氏菌和2株甲型副伤寒沙门氏菌(MICS>；4 mg/L)与环丙沙星敏感性降低(MICS 0.125-1 mg/L)菌株进行比较。结果：在伤寒沙门氏菌和甲型副伤寒沙门氏菌中，存在一个单一的GyrA突变(Ser-83>；)。Phe或Ser-83-&Gt；Tyr)与环丙沙星敏感性降低(MIC 0.125-1 mg/L)相关；ParC的另一个突变(Ser-80-&Gt；Ile，Ser-80-&Gt；Arg，Asp-69-&Gt；Glu或Gly-78-&Gt；Asp)伴随着环丙沙星MIC的增加(>；=0.5 mg/L)。三个突变导致环丙沙星耐药：两个在gyrA(Ser-83-&Gt；Phe和Asp-87-&Gt；Asn或Asp-87-&Gt；Gly)，一个在ParC。这是伤寒沙门氏菌ParC基因突变的首次报道。耐环丙沙星伤寒沙门菌和甲型副伤寒沙门菌的最低抑菌浓度不同，gyrA和parC基因突变也不同。此外，伤寒沙门氏菌携带1类整合子(dfrA15/aadA1)的50kb可转移质粒对复方新诺明和四环素耐药，但对环丙沙星不耐药。在耐环丙沙星伤寒沙门菌和甲型副伤寒沙门菌中，PFGE均显示出难以区分的XbaI片段模式，显示耐环丙沙星伤寒沙门菌是从一株对环丙沙星敏感性降低的克隆性相关分离株中分离出来的。结论：据我们所知，这是首次报道对环丙沙星完全耐药的伤寒沙门菌的分子特征。值得注意的是，在对环丙沙星耐药的伤寒沙门氏菌中存在质粒型整合子，可能会导致无法治愈的肠热病。
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 (>= 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.