Unraveling the Genomic Landscape of Staphylococcus aureus in Hospital Settings of East Africa

Background Staphylococcus aureus is a major pathogen that causes hospital- and community-acquired infections, with increasing antimicrobial resistance (AMR) posing a global threat. East Africa remains an understudied region concerning the genomic epidemiology of S. aureus. This study provides a comprehensive genomic characterization of S. aureus genomes from hospital settings in East Africa, focusing on AMR, virulence determinants, mobile genetic elements (MGEs), and population structure. Methods We analyzed a total of 496 S. aureus whole-genome sequences (WGSs) from Tanzania, Kenya and Uganda retrieved from the NCBI Sequence Read Archive (SRA). Bioinformatics pipelines were employed for quality control, genome assembly, annotation and comparative genomics. In-silico multi-Locus Sequence Typing (MLST), spa & SCCmec typing and pangenome assessment were conducted. AMR and virulence genes, as well as plasmid and prophage diversity, were identified via curated databases. Results MLST analysis revealed 45 sequence types (STs), including 18 novel allelic profiles, with CC152 (ST152) being the most prevalent (26.7%). Spa typing identified 67 distinct types, with t355 (24.4%) and t1476 (17.8%) dominating. SCCmec typing revealed Type V (78.1%) as the predominant methicillin resistance determinant, particularly in Tanzania (91.3%). AMR profiling revealed 94 resistance genes, with a high prevalence of blaZ (β-lactamase), tet(38) (tetracycline efflux), and dfrG (trimethoprim resistance). Virulence gene analysis revealed 147 loci, including Panton-Valentine leukocidin (lukF-PV; 2.1%) and biofilm-associated genes (icaD). Plasmid analysis revealed high diversity, with Tanzania exhibiting the highest replicon complexity (mean = 4.2 plasmids/isolate). The phage sequence (n = 934) was predominantly Siphoviridae (94.1%), with no significant geographic structuring. Pangenome analysis revealed extreme diversity, with only five core genes conserved across all the isolates and 68,759 strain-specific cloud genes. Conclusion This study highlights the dynamic genomic landscape of S. aureus in East Africa, characterized by regional clonal expansion, extensive AMR, and diverse virulence profiles. The dominance of community-associated MRSA (Type V SCCmec) in Tanzania contrasts with Kenya’s co-circulation of hospital and community strains, whereas Uganda harbors rare SCCmec Type VI strains, suggesting potential zoonotic origins. These findings emphasize the need for region-specific surveillance and tailored AMR stewardship programs to mitigate the spread of resistant and virulent S. aureus clones in East Africa.