Department of Clinical Laboratory, Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.
Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), No. 1 Jiazi Road, Lunjiao, Shunde District, Foshan City, Guangdong Province, China.
J Antimicrob Chemother. 2024 Oct 1;79(10):2688-2697. doi: 10.1093/jac/dkae281.
Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates.
A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study.
The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1-AR5) recognized at different times and departments were closely related [3-74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph(A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS26-class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph(A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli, Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph(A) in 10 NTS isolates was IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids.
These findings highlighted that the dissemination of these plasmids carrying mph(A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections.
非伤寒沙门氏菌（NTS）对阿奇霉素耐药的机制鲜有报道。本研究旨在探讨 10 株耐阿奇霉素 NTS 的流行病学和遗传特征。
本研究共收集了来自广州一家三甲医院的 457 株 NTS 分离株。我们进行了药敏试验、接合实验、外排泵表达试验、全基因组测序和生物信息学分析。
结果显示，10 株 NTS 分离株（2.8%）对阿奇霉素耐药，最小抑菌浓度范围为 128-512mg/L，表现出多重耐药性。系统发育树显示，5 株不同时间和科室分离的伦敦沙门氏菌（AR1-AR5）密切相关[3-74 个单核苷酸多态性（SNP）]，2 株鼠伤寒沙门氏菌（AR7 和 AR8）在 3 个月间隔内为克隆株（<3 SNP）。mph(A)基因位于不同质粒上，包括 IncFIB、IncHI2、InFII、IncC 和 IncI 质粒，赋予了阿奇霉素耐药性。其中，IncFIB、InFII 和 IncHI2 质粒携带不同的 IS26 类 1 整合子（intI1）排列模式，介导了多重耐药基因的传播。可移动的 IncC 质粒编码对环丙沙星、头孢曲松和阿奇霉素的耐药性。此外，系统发育分析表明，mph(A)阳性质粒与本研究中的 10 个质粒密切相关，主要发现于 NTS、大肠杆菌、肺炎克雷伯菌和阴沟肠杆菌中。10 株 NTS 分离株中 mph(A)的遗传环境为 IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26，与不同质粒上的 intI1 共同排列，携带多种耐药基因盒。
这些发现表明，这些携带 mph(A)和各种 intI1 多药耐药基因盒的质粒的传播，将严重限制治疗 NTS 感染的重要抗菌药物的可获得性。
