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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来源期刊
Gene Reports
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.
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