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奇异变形杆菌的基因组分析:揭示全球流行病学和抗菌药物耐药性传播——对公共卫生和生物安全的新挑战

Genomic analysis of Proteus mirabilis: Unraveling global epidemiology and antimicrobial resistance dissemination - emerging challenges for public health and biosecurity.

作者信息

Zhang Shaqiu, Li Qianlong, Wang Mingshu, Jia Renyong, Chen Shun, Liu Mafeng, Zhu Dekang, Zhao Xinxin, Wu Ying, Yang Qiao, Huang Juan, Ou Xumin, Sun Di, Tian Bin, He Yu, Wu Zhen, Cheng Anchun

机构信息

Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Institute of Veterinary Medicine and Immunology, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, PR China.

Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China.

出版信息

Environ Int. 2025 May;199:109487. doi: 10.1016/j.envint.2025.109487. Epub 2025 Apr 18.

DOI:10.1016/j.envint.2025.109487
PMID:40273554
Abstract

Given the escalating public health threat posed byProteus mirabilis(P. mirabilis) and its rapidly evolving drug resistance, it is imperative to elucidate its global epidemiology and resistance mechanisms through a comprehensive genomic lens. As of August 2024, 3,403 high-qualityP. mirabilisgenomes were retrieved from public databases (total 3,752), spanning 58 countries/regions, with the United States showing the highest report rate (52.51 %). Human-derived isolates, particularly from urine (34.47 %), were the primary source. A total of 239 antibiotic resistance genes (ARGs) were identified in P. mirabilis, with β-lactamase and carbapenemase genes being particularly widespread and isolates from China harboring the highest ARG counts. Globally,P. mirabilisisolates were categorized into 17 distinct clusters, with U.S. isolates showing the widest phylogenetic spread. Minimal SNP variations among isolates from different countries and hosts suggest transnational and cross-host clonal propagation. Frequent clonal transmission was also observed among diverse hosts and clinical sources.P. mirabiliscarries numerous integrative and conjugative elements (ICEs), some facilitating ARG dissemination (n = 215). Prophages, though ubiquitous, contributed minimally to ARG spread. Spearman's analysis revealed significant correlations between ARGs and insertion sequences (ISs), replicons, and ICEs. Ancestral state analysis indicated prophages were mainly acquired horizontally, while other mobile genetic elements (MGEs) were largely clonally transmitted. This study provides the first comprehensive genomic analysis ofP. mirabilis's global resistance landscape, highlighting the need to designate it as a novel antimicrobial resistance indicator and implement long-term surveillance.

摘要

鉴于奇异变形杆菌(P. mirabilis)对公共卫生构成的威胁不断升级及其耐药性的迅速演变,有必要通过全面的基因组视角阐明其全球流行病学和耐药机制。截至2024年8月,从公共数据库(共3752个)中检索到3403个高质量的奇异变形杆菌基因组,覆盖58个国家/地区,美国的报告率最高(52.51%)。人源分离株,尤其是尿液中的分离株(34.47%)是主要来源。在奇异变形杆菌中总共鉴定出239个抗生素抗性基因(ARGs),其中β-内酰胺酶和碳青霉烯酶基因特别普遍,来自中国的分离株携带的ARGs数量最多。在全球范围内,奇异变形杆菌分离株被分为17个不同的簇,美国分离株的系统发育分布最广。不同国家和宿主的分离株之间最小的单核苷酸多态性变异表明存在跨国和跨宿主的克隆传播。在不同宿主和临床来源之间也观察到频繁的克隆传播。奇异变形杆菌携带大量整合和接合元件(ICEs),其中一些促进了ARGs的传播(n = 215)。噬菌体虽然普遍存在,但对ARGs传播的贡献最小。Spearman分析显示ARGs与插入序列(ISs)、复制子和ICEs之间存在显著相关性。祖先状态分析表明噬菌体主要是通过水平方式获得的,而其他移动遗传元件(MGEs)主要是通过克隆方式传播的。本研究首次对奇异变形杆菌的全球耐药格局进行了全面的基因组分析,强调了将其指定为新型抗菌药物耐药性指标并实施长期监测的必要性。

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