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中国东南部福建省 2005-2019 年临床分离株的基因组和抗生素耐药特征。

Genome and antibiotic resistance characteristics of clinical isolates in Fujian Province, Southeast China, 2005-2019.

机构信息

Fujian Center for Disease Control and Prevention, Fuzhou, PR China.

Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, PR China.

出版信息

Microb Genom. 2024 Nov;10(11). doi: 10.1099/mgen.0.001325.

DOI:10.1099/mgen.0.001325
PMID:39565081
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11893363/
Abstract

Shigellosis is a serious public health issue in many developing countries. The emergence of multidrug-resistant (MDR) isolates has deepened the treatment difficulty and health burden of shigellosis. China is the largest developing country in the world, but so far, the genome of MDR isolates has not been well characterized. In this study, 60 clinical isolates of spp. in Fujian Province, southeast China, from 2005 to 2019 were characterized for drug resistance phenotype, whole-genome sequencing and bioinformatics analysis. The results showed that the MDR rate of isolates was 100%, among which the resistance rates of cefotaxime, ciprofloxacin and azithromycin were 36.67, 21.67 and 10.00 %, respectively. The positive rate of extended-spectrum beta-lactamase (ESBL)-producing strains was 23.33%. The resistance profiles of and to some antimicrobials differed. The MDR isolates carried multiple antimicrobial resistance genes, among which and mediated ESBL resistance '' (type I) and '' (type II) were the most common genetic environments around the genes, and plasmids containing these structures included IncFII, IncI1, IncI2 and IncN. The double gene mutation pattern of A and C resulted in a significant decrease in the sensitivity of to ciprofloxacin. The overall resistance phenotype and genotype concordance rate was 88.50%, and the sensitivity and specificity of the genotype antimicrobial susceptibility test (AST) were 93.35 and 82.53 %, respectively. However, inconsistency occurred between phenotypic and genotype profiles for a few antibiotics. Phylogenomic investigation with core genome multi-locus sequence typing (cgMLST) and SNPs were used to characterize the endemic transmission of these infections in Fujian and their evolutionary origin within the global context. For , Fujian isolates were all limited to PG3 and could be divided into three phylogenetic clusters. The ciprofloxacin-resistant strains were mainly F2a and FXv and assigned to the three clusters with different quinolone resistance-determining region mutation patterns. For , most Fujian strains belonged to Lineage III with genotype 3.7.6, except three isolates of Lineage I with genotype 1.3. The strains carrying the genes were dispersed, indicating different origins of gene acquisition. Most of the circulating isolates in Fujian Province were not related to major international outbreak lineages and were only endemic to the country. In conclusion, multi-drug resistance of isolates in Fujian Province was serious, and genome-based laboratory surveillance will be crucial to the clinical treatment and public health measures for shigellosis.

摘要

志贺菌病是许多发展中国家的严重公共卫生问题。多药耐药(MDR)分离株的出现加深了志贺菌病的治疗难度和健康负担。中国是世界上最大的发展中国家,但迄今为止,MDR 分离株的基因组尚未得到很好的描述。本研究对 2005 年至 2019 年来自中国东南部福建省的 60 株 spp.临床分离株进行了耐药表型、全基因组测序和生物信息学分析。结果表明, 分离株的 MDR 率为 100%,其中头孢噻肟、环丙沙星和阿奇霉素的耐药率分别为 36.67%、21.67%和 10.00%。产超广谱β-内酰胺酶(ESBL)菌株的阳性率为 23.33%。 和 对某些抗菌药物的耐药谱不同。MDR 分离株携带多种抗菌药物耐药基因,其中 和 介导的 ESBL 耐药 ''(I 型)和 ''(II 型)是 基因周围最常见的遗传环境,包含这些结构的质粒包括 IncFII、IncI1、IncI2 和 IncN。A 和 C 的双基因突变模式导致 对环丙沙星的敏感性显著降低。总体耐药表型和基因型一致性率为 88.50%,基因型抗菌药物敏感性试验(AST)的敏感性和特异性分别为 93.35%和 82.53%。然而,少数抗生素的表型和基因型谱之间存在不一致性。利用核心基因组多位点序列分型(cgMLST)和单核苷酸多态性(SNP)进行的系统发育基因组学研究,对福建省这些感染的地方性传播及其在全球范围内的进化起源进行了描述。对于 ,福建分离株均局限于 PG3,可分为三个进化枝。耐环丙沙星菌株主要为 F2a 和 FXv,在不同的喹诺酮类药物耐药决定区突变模式下被分到三个进化枝中。对于 ,大多数福建菌株属于基因型为 3.7.6 的 III 谱系,除了三个 I 谱系的菌株基因型为 1.3。携带 基因的菌株分散存在,表明基因获得的来源不同。福建省流行的分离株大多与主要的国际暴发谱系无关,仅在国内流行。总之,福建省 分离株的多药耐药性严重,基于基因组的实验室监测对于志贺菌病的临床治疗和公共卫生措施至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3d/11893363/9fbefef4d11e/mgen-10-01325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3d/11893363/0a42a07e1d1d/mgen-10-01325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3d/11893363/9fbefef4d11e/mgen-10-01325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3d/11893363/0a42a07e1d1d/mgen-10-01325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3d/11893363/9fbefef4d11e/mgen-10-01325-g002.jpg

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