Whole genome sequencing reveals virulence-mobile element linkages and phylogenetic diversity in multidrug-resistant Escherichia coli from Nigeria.

IF 4 2区生物学 Q2 MICROBIOLOGY

Frontiers in Microbiology Pub Date : 2025-05-07 eCollection Date: 2025-01-01 DOI:10.3389/fmicb.2025.1579175

Nubwa Medugu, Mabel Kamweli Aworh, Kenneth Iregbu, Philip Nwajiobi-Princewill, Dawn M Hull, Lyndy Harden, Pallavi Singh, Stephen Obaro, Abiodun Egwuenu, Faith Adeboye, Ruth Egah, Leonard Uzairue, Yahaya Mohammed, Nwafia Ifeyinwa, Siddhartha Thakur

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Abstract

Background: Multidrug-resistant Escherichia coli poses a critical public health threat in Nigeria, where limited genomic surveillance hinders the understanding of virulence-resistance interplay.

Methods: This cross-sectional study employed whole-genome sequencing to characterize 107 MDR-E isolates from a Nigerian tertiary hospital (2019-2020), analyzing virulence genes, mobile genetic elements (MGEs), phylogroups, sequence types (STs), pathotypes, and antimicrobial resistance (AMR).

Results: We identified 2,021 virulence genes across nine functional categories, dominated by immune evasion (terC, 96.3%), adherence (fimH, 86%), and iron acquisition (fyuA, 63.6%). Strikingly, 81.3% of virulence genes were linked to MGEs, including MITEEc1 (75.7% of isolates) and IS30 (56.1%), with IncFII (17.8%) and Col156 (12.1%) plasmids co-harboring virulence (e.g., traJ/traT, senB) and AMR genes (e.g., blaTEM-1B). Phylogroup B2 (32.7%) dominated, exhibiting high resistance to ampicillin (97.1%) and emerging meropenem resistance (11.4%). Globally disseminated STs (ST131, ST410, ST648) carried significantly more diverse virulence genes than minor clones (p = 0.028) and were strongly associated with double-serine QRDR mutations (gyrA_S83L: 97.6%, parC_S80I: 97.6%), which correlated with more virulence genes (24.2 vs. 22.3 genes) and resistance (MAR index: 0.7 vs. 0.5) compared to minor clones. Notably, 92% (61/66) of high-risk clones harbored these mutations, versus 57% (21/37) of low-risk clones, suggesting a fitness advantage enabling major clones to sustain larger genetic cargoes. Pathotyping revealed 54.2% as extraintestinal pathogenic E. coli (ExPEC), with 72.4% of these being uropathogenic (UPEC) and 5.2% ExPEC/EAEC hybrids, alongside 43.9% atypical ExPEC strains. Hierarchical clustering demonstrated phylogroup B2's genetic diversity and co-localization of plasmid-borne virulence/AMR genes.

Discussion: These findings underscore Nigeria's MDR-E crisis, driven by MGE-facilitated gene transfer, hybrid pathotypes, and globally disseminated high-risk clones harboring double-serine QRDR mutations. There is continued need for robust genomic surveillance, stringent infection control measures, enhanced antibiotic stewardship, and exploration of antivirulence strategies (e.g., targeting fimH or yeh) to curb the spread of these highly adaptable pathogens in resource-limited settings and beyond.

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全基因组测序揭示了尼日利亚多药耐药大肠杆菌的毒力-移动元件联系和系统发育多样性。

背景：耐多药大肠杆菌在尼日利亚构成严重的公共卫生威胁，在尼日利亚，有限的基因组监测阻碍了对毒力-耐药性相互作用的了解。方法：本横断面研究采用全基因组测序方法对尼日利亚某三级医院（2019-2020）107株耐多药e菌株进行了特征分析，分析了毒力基因、移动遗传元件（MGEs）、系统群、序列类型（STs）、病理型和抗微生物药物耐药性（AMR）。结果：我们鉴定了9个功能类别的2021个毒力基因，主要是免疫逃避（terC, 96.3%）、粘附（fimH, 86%）和铁获取（fyuA, 63.6%）。值得注意的是，81.3%的毒力基因与MGEs相关，包括MITEEc1（75.7%的分离株）和IS30 (56.1%), IncFII（17.8%）和Col156（12.1%）质粒共同携带毒力（例如traJ/traT， senB）和AMR基因（例如blatemm - 1b）。系统群B2占主导地位（32.7%），对氨苄西林高耐药（97.1%），新出现的美罗培南耐药（11.4%）。全球传播的STs （ST131、ST410、ST648）携带的毒力基因多样性显著高于小克隆（p = 0.028），与双丝氨酸QRDR突变（gyrA_S83L: 97.6%, parC_S80I: 97.6%）密切相关，与小克隆相比，与更多毒力基因（24.2比22.3个基因）和耐药性（MAR指数：0.7比0.5）相关。值得注意的是，92%（61/66）的高风险克隆携带这些突变，而57%（21/37）的低风险克隆携带这些突变，这表明适应性优势使主要克隆能够维持更大的基因负荷。病理分型显示54.2%为肠外致病性大肠杆菌（exic），其中72.4%为尿路致病性大肠杆菌（UPEC）， 5.2%为exic /EAEC杂交菌株，43.9%为非典型exic菌株。等级聚类表明系统群B2具有质粒携带毒力/抗菌素耐药性基因的遗传多样性和共定位。讨论：这些发现强调了尼日利亚的耐多药- e危机，这是由mge促进的基因转移、杂交病型和全球传播的含有双丝氨酸QRDR突变的高风险克隆造成的。继续需要强有力的基因组监测，严格的感染控制措施，加强抗生素管理，并探索抗毒策略（例如，以h或yeh为目标），以遏制这些高适应性病原体在资源有限环境和其他环境中的传播。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Microbiology MICROBIOLOGY-

CiteScore

7.70

自引率

9.60%

发文量

4837

审稿时长

14 weeks

期刊介绍： Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.