High clonal diversity, resistome, and virulome of Escherichia coli causing sepsis in Ethiopian tertiary hospitals: a multicenter genomic study.

BACKGROUND: WHO-priority multidrug-resistant (MDR) Escherichia coli poses major global health challenges, especially in low- and middle-income countries. METHODS: From October 2019 to September 2020, a multicenter study was conducted at Tikur Anbessa Specialized Hospital (TASH) and Yekatit 12 Hospital Medical College (Y12HMC) in the central region, Hawassa University Comprehensive Specialized Hospital (HUCSH) in the south, and Dessie Comprehensive Specialized Hospital (DCSH) in the north, analyzing 1,416 blood cultures from suspected sepsis patients. E. coli isolates were identified by MALDI-TOF, and whole-genome sequencing was performed using Illumina HiSeq 2,500. RESULTS: A total of 53 E. coli isolates from sepsis patients were collected from TASH (n = 28), DCSH (n = 17), HUCSH (n = 4), and Y12HMC (n = 4). The isolates exhibited high clonal diversity, comprising 24 distinct STs, including several internationally recognized high-risk clones such as ST131, ST167, ST410, ST405, ST648, ST69, and ST10. Phenotypically, 79% (n = 42/53) of these isolates were multidrug-resistant (MDR), and genome analysis revealed numerous acquired resistance genes and mutations, with unique clustering patterns for each hospital. β-lactam resistance genes were identified in 98% (n = 52/53) of isolates, and the ESBL gene bla CTX-M-15 was detected in 49% (n = 26/53). Resistance genes for quinolones (gyrA_S83L, parC_S80I, gyrA_D87N, parE_S458A, parE_I529L, parC_E84V), tetracycline (tet(A), tet(B)), and trimethoprim (dfrA1, dfrA12, dfrA14, dfrA17, dfrA19, dfrA8) were found in 60% (n = 32/53). Resistance genes for streptomycin (aadA5, aph(6)-Id, aph(3″)-Ib), sulfonamides (sul1, sul2), macrolides (mph(A)), and gentamicin (aac(3)-IIe, aac(3)-IId) were present in 60%(n = 32/53), 59%(n = 31/53), 53%(n = 28/53), and 38%(n = 20/53) of E. coli isolates, respectively. AMR genes resided on diverse plasmids (IncFII, IncFIB, IncFIA, IncI, ColRNAI, IncQ), with bla CTX-M-15 specifically linked to IncFIB (H89-PhagePlasmid). Plasmids also carried multiple virulence factors, including adhesins, iron-acquisition systems, toxins, serum resistance factors, protectins, and others. CONCLUSION: High-risk, diverse E. coli strains containing multiple AMR and virulence genes, along with plasmids, were common among patients with sepsis in Ethiopia. This highlights the need for strengthened infection control, better antimicrobial stewardship, and expanded microbiological and genomic monitoring to fight antimicrobial resistance.