Genome sequencing and biostatistical analysis revealed genomic hotspots for evolution of hospital-associated Staphylococcus aureus in Western Kenya hospitals.

Nyabera, M. N.*, Sifuna, A., Okoth, P.

Department of Biological sciences, Masinde Muliro University of Science and Technology, Kakamega, Kenya

Staphylococcus aureus is a clinically significant pathogen often associated with high levels of antimicrobial resistance (AMR). While genomic advancements have shed light on AMR mechanisms in developed countries, little is known about S. aureus biology and epidemiology in less-developed regions like sub-Saharan Africa. This knowledge gap needs urgent attention since S. aureus's role in wound infections, pneumonia, urinary tract infections, and bacteraemia has been attributed to healthcare burden in hospitals. In our recent work, we analyzed a collection of S. aureus recovered from both hospital-acquired infections and community-acquired infections at a referral hospital in Kakamega, Western Kenya. This facility has an established antimicrobial stewardship (AMS) program, but like in many similar facilities in sub-Saharan Africa, the program is poorly funded and does not function optimally. Consequently, pathogens such as S. aureus remain a significant healthcare and infection problem. Recent advances in next-generation sequencing and bioinformatics processing of large arrays of sequence data may facilitate improvements in antimicrobial resistance stewardship in low-income African countries. We isolated a collection of S. aureus from surgical site infections (SSIs), characterized their antimicrobial resistance profiles, and performed whole-genome sequencing and genome analyses using state-of-the-art bioinformatics tools, including our in-house pipeline for contig gap closure and standard software tools for the identification of pathogenicity genes: Abricate, RGI, and SeqWord Genomic Island Sniffer. Our data revealed evolutionary segregation in closely-related lineages of S. aureus and provided insights into their genetic diversity and relatedness. Antimicrobial susceptibility testing identified strains resistant to multiple antibiotics, including cephalosporins and oxacillin. Genotyping and phylogenetic analysis revealed strain-specific differences and distinct clusters among hospital- and community-acquired isolates. Moreover, plasmid analysis revealed conserved homologous plasmids across ST152 isolates and identified key virulence and resistance genes. We also identified horizontally transferred genetic islands, suggesting active mechanisms of genetic acquisition and adaptation. Overall, this study outlines the genomic landscape of S. aureus in a Kenyan hospital setting, offering valuable insights into antimicrobial resistance (AMR), virulence, and transmission dynamics. These findings underscore the need for tailored infection control strategies and evidence-based clinical practices to address the growing threat of S. aureus infections in sub-Saharan Africa.

Keywords: Staphylococcus aureus, bioinformatics, phylogenetics