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印度携带质粒介导的AmpCβ-内酰胺酶CMY6的第三代头孢菌素耐药性肠炎沙门氏菌巴雷利ST203临床分离株的首次报告:基因组特征和传播性

First report of third-generation cephalosporin-resistant clinical isolate of Salmonella Bareilly ST203 harbouring plasmid-mediated AmpC β-lactamase CMY6 from India: Genome characteristics and transmissibility.

作者信息

Roy Subhasree, Majumdar Agniva, Nandy Souvik, Pal Juhi, Veeraraghavan Balaji, Walia Kamini, Dutta Shanta

机构信息

Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI), Kolkata, India.

Division of Virology, ICMR-National Institute for Research in Bacterial Infections (ICMR-NIRBI), Kolkata, India.

出版信息

Infect Genet Evol. 2025 Jun;130:105736. doi: 10.1016/j.meegid.2025.105736. Epub 2025 Mar 6.

DOI:10.1016/j.meegid.2025.105736
PMID:40057151
Abstract

Non-typhoidal Salmonella (NTS) infections are a major public health concern in India because of inadequate knowledge of antimicrobial resistance, limiting therapeutic options. The study aimed to characterize and analyse the genome of a 3rd-generation cephalosporins (3GCs)-resistant clinical isolate of Salmonella Bareilly-harbouring plasmid-mediated AmpC (pAmpC) CMY-6. Identification, antibiotic susceptibility and Whole Genome Sequencing (WGS)-based analysis were performed. Transmissibility, replicon types of bla-harbouring plasmid were evaluated. S. Bareilly ST203 (Clonal-Complex 206.2) was isolated from clinical specimen of a paediatric patient and was found to be multidrug-resistant with resistance to 3rd generation cephalosporins, fluoroquinolone and aminoglycosides. WGS revealed pAmpC bla on conjugative IncC plasmid (158,385 kb) which successfully transferred into the transconjugant with other resistance determinants (bla, armA, aac(6')-Ib-cr, sul1), showed higher MICs for 3GCs. Downstream regions of bla include blc (lipocalin), sugE (efflux protein) and truncated ecnR (entericidin R) followed by other resistance genes. Presence of ISEcp1 in the genome facilitated the transfer of bla Several efflux pump genes, two complete CRISPR arrays and intact phage sequences were also detected. Virulence factors associated with Salmonella Pathogenicity Islands SPI-1/SPI-2/SP-3 and their effectors indicated the virulence potential of this strain. To the best of our knowledge, genome of a 3GCs-resistant clinical isolate of S. Bareilly-harbouring pAmpC bla was reported and analysed for the first time in this study. S. Bareilly was found to cause outbreaks in earlier reports but lower resistance was reported in this serovar compared to other NTS. As infections by NTS are concerning, early detection of such strains is of utmost importance.

摘要

由于对抗菌药物耐药性的认识不足,限制了治疗选择,非伤寒沙门氏菌(NTS)感染成为印度主要的公共卫生问题。本研究旨在对携带质粒介导的AmpC(pAmpC)CMY-6的第三代头孢菌素(3GCs)耐药的临床分离株——巴雷利沙门氏菌的基因组进行表征和分析。进行了鉴定、抗生素敏感性试验以及基于全基因组测序(WGS)的分析。评估了携带bla的质粒的可转移性和复制子类型。从一名儿科患者的临床标本中分离出巴雷利沙门氏菌ST203(克隆复合体206.2),发现其对第三代头孢菌素、氟喹诺酮类和氨基糖苷类耐药,具有多重耐药性。WGS显示在接合型IncC质粒(158,385 kb)上存在pAmpC bla,该质粒与其他耐药决定簇(bla、armA、aac(6')-Ib-cr、sul1)成功转移到了接合子中,对3GCs显示出更高的最低抑菌浓度(MIC)。bla的下游区域包括blc(脂钙素)、sugE(外排蛋白)和截短的ecnR(肠杀菌素R),随后是其他耐药基因。基因组中ISEcp1的存在促进了bla的转移。还检测到了几个外排泵基因、两个完整的CRISPR阵列和完整的噬菌体序列。与沙门氏菌致病岛SPI-1/SPI-2/SP-3相关的毒力因子及其效应子表明了该菌株的毒力潜力。据我们所知,本研究首次报道并分析了携带pAmpC bla的3GCs耐药的巴雷利沙门氏菌临床分离株的基因组。在早期报告中发现巴雷利沙门氏菌会引起暴发,但与其他NTS相比,该血清型的耐药性较低。由于NTS感染令人担忧,尽早检测出此类菌株至关重要。

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