Whole genome sequencing reveals virulence-mobile element linkages and phylogenetic diversity in multidrug-resistant from Nigeria.

Background: Multidrug-resistant poses a critical public health threat in Nigeria, where limited genomic surveillance hinders the understanding of virulence-resistance interplay.

Methods: This cross-sectional study employed whole-genome sequencing to characterize 107 MDR-E isolates from a Nigerian tertiary hospital (2019-2020), analyzing virulence genes, mobile genetic elements (MGEs), phylogroups, sequence types (STs), pathotypes, and antimicrobial resistance (AMR).

Results: We identified 2,021 virulence genes across nine functional categories, dominated by immune evasion (, 96.3%), adherence (, 86%), and iron acquisition (, 63.6%). Strikingly, 81.3% of virulence genes were linked to MGEs, including MITEEc1 (75.7% of isolates) and IS30 (56.1%), with IncFII (17.8%) and Col156 (12.1%) plasmids co-harboring virulence (e.g., , ) and AMR genes (e.g., ). Phylogroup B2 (32.7%) dominated, exhibiting high resistance to ampicillin (97.1%) and emerging meropenem resistance (11.4%). Globally disseminated STs (ST131, ST410, ST648) carried significantly more diverse virulence genes than minor clones ( = 0.028) and were strongly associated with double-serine QRDR mutations (: 97.6%, : 97.6%), which correlated with more virulence genes (24.2 vs. 22.3 genes) and resistance (MAR index: 0.7 vs. 0.5) compared to minor clones. Notably, 92% (61/66) of high-risk clones harbored these mutations, versus 57% (21/37) of low-risk clones, suggesting a fitness advantage enabling major clones to sustain larger genetic cargoes. Pathotyping revealed 54.2% as extraintestinal pathogenic (ExPEC), with 72.4% of these being uropathogenic (UPEC) and 5.2% ExPEC/EAEC hybrids, alongside 43.9% atypical ExPEC strains. Hierarchical clustering demonstrated phylogroup B2's genetic diversity and co-localization of plasmid-borne virulence/AMR genes.

Discussion: These findings underscore Nigeria's MDR-E crisis, driven by MGE-facilitated gene transfer, hybrid pathotypes, and globally disseminated high-risk clones harboring double-serine QRDR mutations. There is continued need for robust genomic surveillance, stringent infection control measures, enhanced antibiotic stewardship, and exploration of antivirulence strategies (e.g., targeting or ) to curb the spread of these highly adaptable pathogens in resource-limited settings and beyond.