Genomic insight into the high-risk hypervirulent multidrug resistant enteroaggregative-hemorrhagic Escherichia coli ST648/*a194 (serotype O8:H4) isolated from a 3-year-old patient with bloodstream infection in Uganda, sub-Saharan Africa

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-03-14 DOI:10.1016/j.genrep.2025.102198

Reuben S. Maghembe , Maximilian A.K. Magulye , Abdalah Makaranga , Samweli Bahati , Deogratius Mark , Simon Sekyanzi , AbdulGaniy B. Agbaje , Emmanuel Eilu , Savannah Mwesigwa , Eric Katagirya

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Abstract

Gastrointestinal and bloodstream infections account for a major cause of medical emergency and mortality among pediatric populations. Although Escherichia coli is implicated in multiple infections, its virulence and antimicrobial resistance are elusive. Here we aimed to uncover the pathogen associated with diarrhea and sepsis from a 3-year-old patient under ICU in Kampala. We isolated an E. coli strain, challenged it with a panel of 16 antibiotics and whole-genome sequenced it to delve into the virulome and resistome underlying the pathogenicity and relevance to the patient's disease. Antibiotic susceptibility test (AST) results revealed that the isolate was resistant to 12 antibiotics. Combining PathogenFinder with multilocus sequence typing (MLST), we found a high-risk human pathogen (p = 99.9 %), ST648/*a194 (serotype O8:H4), which possesses autotransporters ehaB and enteroaggregative immunoglobulin repeat protein eaeX, among other virulence factors. This strain has acquired plasmids harboring multidrug resistance genes of the beta lactamase family (blaTEM-1B, blaCTX-M-15, and blaOXA-1), aminoglycoside resistance genes including aadA5, aac(3)-IIa and aac(6′)-Ib-cr, and fluroquinolone resistance gene aac(6′)-Ib-cr. Using the comprehensive antibiotic resistance database (CARD), we identified multiple nonsynonymous mutations for the genes gyrA (D87N), S83L, ParC (S80I), conferring fluroquinolone resistance along with the multidrug resistance gene AcrAB-TolC with MarR mutations (Y137H, G103S). Overall, we infer a hybrid pathotype of enteroaggregative-hemorrhagic E. coli (EAHEC) with the potential for gastrointestinal tract, systemic infection and multidrug resistance covering third-generation cephalosporins. Comprehensive genomic surveillance is urgently required to enhance our therapeutic intervention of these high-risk E. coli clones in low-resource settings.

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从撒哈拉以南非洲乌干达一名3岁血液感染患者中分离出的高风险高毒性多药耐药肠聚集出血性大肠杆菌ST648/*a194（血清型O8:H4）的基因组分析

胃肠道和血流感染是儿童医疗急救和死亡的主要原因。虽然大肠杆菌与多种感染有关，但其毒力和抗菌素耐药性难以捉摸。在这里，我们的目的是揭示与腹泻和败血症相关的病原体从一个3岁的病人在坎帕拉ICU。我们分离出一株大肠杆菌，用16种抗生素对其进行挑战，并对其进行全基因组测序，以深入研究致病性和与患者疾病相关的病毒组和抵抗组。抗生素药敏试验（AST）结果显示该菌株对12种抗生素耐药。结合pathgenfinder和多位点序列分型（multilocus sequence typing， MLST），我们发现了一种高风险的人病原体ST648/*a194（血清型O8:H4），其具有自身转运蛋白ehaB和肠聚集免疫球蛋白重复蛋白eaeX等毒力因子。该菌株获得了含有β -内酰胺酶家族多药耐药基因（blatemm - 1b、blaCTX-M-15和blaOXA-1）的质粒，氨基糖苷类耐药基因包括aadA5、aac(3)-IIa和aac（6’）-Ib-cr，以及氟喹诺酮类耐药基因aac（6’）-Ib-cr。利用综合抗生素耐药数据库（CARD），我们鉴定出gyrA （D87N）、S83L、ParC （S80I）基因的多个非同义突变，与具有MarR突变（Y137H、G103S）的多药耐药基因acrabb - tolc一起赋予氟喹诺酮类药物耐药性。总的来说，我们推断肠聚集出血性大肠杆菌（EAHEC）具有胃肠道、全身感染和覆盖第三代头孢菌素的多药耐药的潜力。迫切需要全面的基因组监测，以加强我们在低资源环境中对这些高风险大肠杆菌克隆的治疗干预。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.