PathoGenomics of Multidrug-Resistant Escherichia coli from Bloodstream Infections in South Africa

Background: Escherichia coli ( E. coli ) is a leading cause of bloodstream infections (BSIs) globally, with multidrug-resistant (MDR) strains complicating treatment outcomes. In South Africa, genomic data on such isolates remain scarce. Objectives: To elucidate the genomic landscape of E. coli isolates from bloodstream infections (BSIs) collected over a one-year period in the uMgungundlovu District, South Africa, with a focus on the resistome, virulome, mobile genetic elements (MGEs), genetic synteny, sequence types (STs), and phylogenomic context. Methods: Twenty-five non-duplicate E. coli isolates were recovered from blood cultures and subjected to antimicrobial susceptibility testing. All twelve MDR isolates underwent whole-genome sequencing and bioinformatic analysis. Results: The MDR isolates comprised six distinct STs, notably high-risk international lineages ST131 (33.3%) and ST69 (25.0%), spanning five phylogroups, predominantly B2 and D. Eight O:H serotypes were identified, with O25:H4 and O45:H16 being most frequent. CH-typing revealed dominant CH types CH40-30 (ST131) and CH35-27 (ST69) and fimH alleles such as fimH30 and fimH27 . The isolates encoded βeta-lactamases, including bla _CTX-M-15 , bla _TEM-1B and bla _OXA-1, frequently co-located with MGEs. Notably, bla _CTX-M-15 was chromosomally integrated within a Tn 3 –IS Ec9 transposon unit, while bla _TEM-1B and bla _OXA-1 were embedded in diverse plasmid-associated syntenic architectures flanked by IS 1 , IS 91 , or integron-associated regions. Other resistome were detected, conferring resistance to aminoglycosides ( aph(3')-Ia , aac(3)-IIa , aac(3)-IIe , aadA1 , aadA2 ), sulfonamides ( sul1 , sul2 ) and trimethoprim ( dfrA variants). A diverse array of virulome was identified, associated with adhesion, iron acquisition, serum resistance, and toxin production. Phylogenomic clustering revealed close relationships between local ST131/ST69 isolates and counterparts across Africa, highlighting regional clonal dissemination. Conclusion: The study identifies diverse MDR E. coli clones circulating in bloodstream infections, notably high-risk lineages ST131, ST69 and ST10, with complex resistomes and virulome arsenals facilitated by MGEs. These insights reinforce the imperative for genomic surveillance to guide infection control and antibiotic stewardship in high-burden settings.