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基于全基因组测序的临床复合体的物种分类、多位点序列分型及抗生素耐药机制

Whole-genome sequencing-based species classification, multilocus sequence typing, and antibiotic resistance mechanisms of the clinical complex.

作者信息

Lu Junwan, Zhang Lei, Yan Chunxia, Lin Naru, Zhang Yuan, Sha Yuning, Zhao Jingxuan, Lu Jun, Bao Qiyu, Zhang Guozhi

机构信息

Medical Molecular Biology Laboratory, School of Medicine, Jinhua University of Vocational Technology, Jinhua, China.

Department of Clinical Laboratory, Quzhou People's Hospital/The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China.

出版信息

Front Microbiol. 2025 Feb 25;16:1473150. doi: 10.3389/fmicb.2025.1473150. eCollection 2025.

DOI:10.3389/fmicb.2025.1473150
PMID:40071199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11893600/
Abstract

BACKGROUND

Multidrug-resistant strains of the genus can produce various β-lactamases that confer resistance to a broad spectrum of β-lactams, which poses a significant public health threat due to their emergence and spread in clinical settings and natural environments. Therefore, a comprehensive investigation into the antibiotic resistance mechanisms of is scientifically significant.

METHODS

Between 2018 and 2021, 78 clinical isolates were collected from human clinical specimens. The MicroScan WalkAway system and average nucleotide identity (ANI) analyses were used to classify the bacterial species. Antibiotic susceptibility was determined through the minimum inhibitory concentration (MIC) test via the agar dilution method. To determine the resistance mechanism and the structure of the resistance gene-related sequences, molecular cloning, whole-genome sequencing and bioinformatic analysis were performed.

RESULTS

Among the 78 isolates studied in this work, obtained from various specimens from different clinical departments, 77 were classified into seven known species by ANI analysis. Most of the isolates were (34.6%, 27/78), followed by (25.6%, 20/78). Multilocus sequence typing (MLST) revealed that they belonged to 72 sequence types (STs), including 52 new STs. A total of 334 resistance genes of 30 antibiotic resistance genotypes were identified from the genomes, more than half (55.99%, 187/334) of which were β-lactamase genes. The isolates showed much higher rates of resistance to penicillins (penicillin G, 98.7%) and first-generation cephalosporins (cefazolin, 96.2%), but lower resistance rates to fourth-generation cephalosporins (cefepime, 6.4%), monobactams (aztreonam, 5.1%), and carbapenems (imipenem, 1.3% and meropenem, 5.1%). Structural analyses of some β-lactamase genes (such as and ) related sequences revealed that they were generally associated with mobile genetic elements.

CONCLUSION

The investigation of the correlation between the distribution of β-lactamase genes and resistance phenotypes in this study suggested an urgent need for rigorous monitoring and control to counteract the escalating public health threat posed by the increase in strains harboring extended-spectrum β-lactamase and metallo-β-lactamase genes.

摘要

背景

该属的多重耐药菌株可产生多种β-内酰胺酶,这些酶可使菌株对多种β-内酰胺类抗生素产生耐药性,由于它们在临床环境和自然环境中的出现和传播,对公众健康构成了重大威胁。因此,全面调查该属的抗生素耐药机制具有重要的科学意义。

方法

2018年至2021年期间,从人类临床标本中收集了78株临床分离株。使用MicroScan WalkAway系统和平均核苷酸同一性(ANI)分析对细菌种类进行分类。通过琼脂稀释法的最低抑菌浓度(MIC)试验确定抗生素敏感性。为了确定耐药机制和耐药基因相关序列的结构,进行了分子克隆、全基因组测序和生物信息学分析。

结果

在本研究中所研究的78株分离株中,这些分离株来自不同临床科室的各种标本,通过ANI分析将77株分为七个已知物种。大多数分离株为某菌(34.6%,27/78),其次是另一菌(25.6%,20/78)。多位点序列分型(MLST)显示它们属于72个序列类型(STs),包括52个新的STs。从基因组中鉴定出30种抗生素耐药基因型的总共334个耐药基因,其中超过一半(55.99%,187/334)是β-内酰胺酶基因。分离株对青霉素(青霉素G,98.7%)和第一代头孢菌素(头孢唑林,96.2%)的耐药率要高得多,但对第四代头孢菌素(头孢吡肟,6.4%)、单环β-内酰胺类抗生素(氨曲南,5.1%)和碳青霉烯类抗生素(亚胺培南,1.3%和美罗培南,5.1%)的耐药率较低。对一些β-内酰胺酶基因(如某基因和另一基因)相关序列的结构分析表明,它们通常与可移动遗传元件相关。

结论

本研究中对β-内酰胺酶基因分布与该菌耐药表型之间相关性的调查表明,迫切需要进行严格的监测和控制,以应对携带超广谱β-内酰胺酶和金属β-内酰胺酶基因的该菌菌株增加所带来的日益严重的公共卫生威胁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec23/11893600/0ad3304ba5bf/fmicb-16-1473150-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec23/11893600/9597a3a22c55/fmicb-16-1473150-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec23/11893600/0ad3304ba5bf/fmicb-16-1473150-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec23/11893600/81dc4aa7f2e9/fmicb-16-1473150-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec23/11893600/0ad3304ba5bf/fmicb-16-1473150-g007.jpg

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