湖南省食源性环丙沙星-头孢噻肟-阿奇霉素共耐药汤卜逊沙门菌分子特征研究

Molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica Serovar Thompson in foodborne diseases in Hunan Province

目的分析湖南省人源和水产动物源环丙沙星-头孢噻肟-阿奇霉素共耐药汤卜逊沙门菌的分子流行特征。方法对湖南省食源性疾病散发病例粪便样本和水产品样本中分离的汤卜逊沙门菌进行环丙沙星-头孢噻肟-阿奇霉素共耐药菌株的筛选与鉴定,使用肉汤稀释法对11种抗菌药进行体外药敏试验,并利用全基因组测序技术分析菌株的耐药机制以及进化关系。结果从粪便样本和水产品样本中共分离到19株汤卜逊沙门菌,其中9株菌对环丙沙星-头孢噻肟-阿奇霉素共耐药。进一步分析发现8株菌检出IncC质粒,携带质粒介导的喹诺酮类药物耐药基因qepA-qnrS1、β-内酰胺酶耐药基因bla_(CMY-2)和大环内酯类耐药基因mph(A);1株检出IncR质粒,携带qnrB4-aac(6′)-Ib-cr、bla_(OXA-10)和mph(A)耐药基因。遗传环境分析发现qnrS1、qepA、mph(A)和bla_(CMY-2)基因可能分别通过插入序列ISKra4、IS91、IS6100和ISEcp1整合到耐药菌的基因组上。基于核心基因组生成的系统发生树表明,人源和水产动物源环丙沙星-头孢噻肟-阿奇霉素共耐药汤卜逊沙门菌属于同一进化分支,具有较近的遗传进化关系。结论湖南省人源和水产动物源样本中检出对环丙沙星-头孢噻肟-阿奇霉素共耐药汤卜逊沙门菌,提示此类多重耐药菌已在人和水产动物之间传播。

Objective To investigate the molecular characteristics of ciprofloxacin-cefotaxime-azithromycin co-resistant Salmonella enterica serovar Thompson(S.Thompson)isolates from sporadic cases of foodborne diseases and aquatic foods in Hunan province.Methods Ciprofloxacin-cefotaxime-azithromycin co-resistant S.Thompson isolates were selected from samples,and broth microdilution method was used to determine the resistance to 11 antibiotics of these isolates in vitro.Whole genome sequencing was used for investigating antimicrobial resistance gene patterns and phylogenetic relationships of strains.Results Nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates were recovered from 19 S.Thompson isolates.Among nine ciprofloxacin-cefotaxime-azithromycin co-resistant isolates,eight of them harbored IncC plasmids,simultaneously carrying plasmid-mediated quinolone resistance(PMQR)genes qepA and qnrS1,β-lactamase resistance gene bla_(CMY-2),azithromycin resistance gene mph(A),and one isolate harbored IncR plasmid,and carried PMQR genes qnrB4 and aac(6′)-Ib-cr,bla_(OXA-10) and mph(A).Genetic environment analysis showed that qnrS1,qepA,mph(A)and bla_(CMY-2) genes might be integrated on genomes of strains by ISKra4,IS91,IS6100 and ISEcp1,respectively.Phylogenetic core genome comparisons demonstrated that ciprofloxacin-cefotaxime-azithromycin co-resistant isolates from patients and aquatic foods were genetically similar and clustered together.Conclusion Ciprofloxacin-cefotaxime-azithromycin co-resistant S.Thompson isolates have been isolated from both human and aquatic food samples,suggesting that the spread of multidrug resistant Salmonella between human and aquatic animals.