Emergence of ciprofloxacin heteroresistance in foodborne Salmonella enterica serovar Agona
Emergence of ciprofloxacin heteroresistance in foodborne Salmonella enterica serovar Agona
复制标题
食源性肠沙门氏菌 Agona 中环丙沙星异抗性的出现
DOI：
10.1093/jac/dkaa288
复制
发表时间：
2020
影响因子：
5.2
通讯作者：
Hong-Xia Jiang
中科院分区：
文献类型：
--
作者：
Chuan-Zhen Zhang;Yan Zhang;Xiao-Min Ding;Xiao-Ling Lin;Xin-Lei Lian;Eleftheria Trampari;Nicholas M Thomson;Huan-Zhong Ding;Mark A Webber;Hong-Xia Jiang
BackgroundBacterial heteroresistance has been increasingly identified as an important phenomenon for many antibiotic/bacterium combinations.ObjectivesTo investigate ciprofloxacin heteroresistance inSalmonellaand characterize mechanisms contributing to ciprofloxacin heteroresistance.MethodsCiprofloxacin-heteroresistantSalmonellawere identified by population analysis profiling (PAP). Target mutations and the presence of PMQR genes were detected using PCR and sequencing. Expression ofacrB,acrFandqnrSwas conducted by quantitative RT–PCR. Competition ability and virulence were also compared using pyrosequencing, blue/white screening, adhesion and invasion assays and aGalleriamodel. Two subpopulations were whole-genome sequenced using Oxford Nanopore and Illumina platforms.ResultsPAP identified oneSalmonellafrom food that yielded a subpopulation demonstrating heteroresistance to ciprofloxacin at a low frequency (10−9to 10−7). WGS and PFGE analyses confirmed that the two subpopulations were isogenic, with six SNPs and two small deletions distinguishing the resistant from the susceptible. Both subpopulations possessed a T57S substitution in ParC and carriedqnrS. The resistant subpopulation was distinguished by overexpression ofacrBandacrF, a deletion withinrsxCand altered expression ofsoxS. The resistant population had a competitive advantage against the parental population when grown in the presence of bile salts but was attenuated in the adhesion and invasion of human intestinal cells.ConclusionsWe determined that heteroresistance resulted from a combination of mutations in fluoroquinolone target genes and overexpression of efflux pumps associated with a deletion inrsxC. This study warns that ciprofloxacin heteroresistance exists inSalmonellain the food chain and highlights the necessity for careful interpretation of antibiotic susceptibility.
