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.

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.