Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204
Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204
复制标题
DOI：
10.1093/jac/dkh122
复制
发表时间：
2004-04-01
影响因子：
5.2
通讯作者：
Cloeckaert, A
中科院分区：
文献类型：
--
作者：
Baucheron, S;Chaslus-Dancla, E;Cloeckaert, A
目的：研究TolC和parC突变在伤寒沙门菌噬菌体DT204型（S. Typhimurium DT204）临床克隆株高水平氟喹诺酮耐药中的作用。方法：首次对缺乏氟喹诺酮类药物耐药靶基因突变的鼠伤寒沙门氏菌DT104易感株进行tolC基因（DeltatolC）的缺失。进一步利用P22转导将该菌株中的DeltatolC转导为具有高水平氟喹诺酮耐药性的鼠伤寒沙门氏菌DT204菌株，该菌株携带多个靶基因突变，包括parC（环丙沙星MIC为32 mg/L）中的一个突变。结果：高氟喹诺酮耐药鼠伤寒沙门氏菌DT204株中tolC缺失导致耐药水平下降（16- 32倍），与先前相同菌株的acrB突变体相同，提示AcrAB-TolC是鼠伤寒沙门氏菌DT204株高氟喹诺酮耐药的主要外排系统。在一些鼠伤寒沙门氏菌DT204 DeltatolC转导剂中，parC （Ser-80—>Ile）突变（位于tolC上游9.3 kb处）的缺失导致对氟喹诺酮类药物的耐药性进一步降低16- 32倍，因此出现了超敏感表型（环丙沙星MIC为0.063 mg/L）。结论：AcrAB-TolC外排系统以及包括parC突变在内的多个靶基因突变似乎是鼠伤寒沙门氏菌DT204高水平氟喹诺酮类药物耐药的必要因素。
Objectives: To study the role of TolC and of parC mutation in high-level fluoroquinolone resistance in clonal clinical strains of Salmonella enterica serotype Typhimurium phage type DT204 (S. Typhimurium DT204).Methods: Deletion of the tolC gene (DeltatolC) was first performed in a susceptible S. Typhimurium DT104 strain lacking target gene mutations involved in fluoroquinolone resistance. P22 transduction was further used to transduce DeltatolC from this strain to a high-level fluoroquinolone-resistant S. Typhimurium DT204 strain carrying several target gene mutations, including one in parC (ciprofloxacin MIC of 32 mg/L).Results: Deletion of tolC in the high-level fluoroquinolone-resistant S. Typhimurium DT204 strain resulted in the same decrease in resistance levels (16- to 32-fold) as shown previously for an acrB mutant of the same strain, suggesting that AcrAB-TolC is the main efflux system involved in high-level fluoroquinolone resistance of S. Typhimurium DT204 strains. In some S. Typhimurium DT204 DeltatolC transductants, concomitant loss of the parC (Ser-80-->Ile) mutation, located similar to9.3 kb upstream of tolC, resulted in a further 16- to 32-fold decrease in resistance levels to fluoroquinolones and thus a hypersusceptible phenotype (ciprofloxacin MIC of 0.063 mg/L).Conclusion: The AcrAB-TolC efflux system, together with multiple target gene mutations, including the parC mutation, appear essential to confer high-level fluoroquinolone resistance in S. Typhimurium DT204.