Tigecycline resistance in Serratia marcescens associated with up-regulation of the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome.
Tigecycline resistance in Serratia marcescens associated with up-regulation of the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome.
复制标题
粘质沙雷氏菌中的替加环素耐药性与 SdeXY-HasF 外排系统的上调相关，对环丙沙星和头孢匹罗也有活性。
DOI：
10.1093/jac/dkp475
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
N. Woodford
中科院分区：
文献类型：
--
作者：
M. Hornsey;M. Ellington;M. Doumith;S. Hudson;D. Livermore;N. Woodford
目标
已知RND型转运蛋白的外排可使几种肠杆菌科细菌对替加环素产生耐药性，我们使用临床分离株和实验室选择的突变株在粘质沙雷氏菌中研究了这种机制的潜力。
方法
通过实时RT-PCR分析RND型外排泵基因的表达。通过体外暴露于替加环素或四环素选择实验室突变体。外排泵基因被含有R6 K γ复制起点的自杀质粒灭活。
结果
较高的替加环素MIC与RND型外排泵基因sdeXY的表达升高相关。sdeY或外膜组分基因的失活使替加环素、四环素、环丙沙星和头孢匹罗的MIC降低至低于菌株NCTC 10211的MIC。四环素选择的实验室突变体也显示sdeXY表达和替加环素MIC增加。
结论
内源性SdeXY-HasF介导的外排的上调与S.随着四环素、环丙沙星和头孢匹罗的MIC升高，粘质杆菌也沿着升高。该外排系统的失活将这些化合物的MIC降低至低于菌株NCTC 10211的MIC。
OBJECTIVES
Efflux by RND-type transporters is known to confer resistance to tigecycline in several Enterobacteriaceae species and we examined the potential of this mechanism in Serratia marcescens using a clinical isolate and laboratory-selected mutants.
METHODS
Expression of RND-type efflux pump genes was analysed by real-time RT-PCR. Laboratory mutants were selected by exposure to either tigecycline or tetracycline in vitro. Efflux pump genes were inactivated by suicide plasmids containing the R6K gamma origin of replication.
RESULTS
Higher tigecycline MICs correlated with elevated expression of the RND-type efflux pump genes sdeXY. Inactivation of sdeY or the outer membrane component gene hasF reduced MICs of tigecycline, tetracycline, ciprofloxacin and cefpirome to below those for strain NCTC 10211. A tetracycline-selected laboratory mutant also showed increases in sdeXY expression and tigecycline MIC.
CONCLUSIONS
Up-regulation of endogenous SdeXY-HasF-mediated efflux is associated with tigecycline resistance in S. marcescens along with MIC rises for tetracycline, ciprofloxacin and cefpirome. Inactivation of this efflux system reduced MICs of those compounds to below those for strain NCTC 10211.