Genomic comparison of Staphylococcus aureus isolates from patients with bacteraemia and infective endocarditis at public hospitals in Gauteng, South Africa.

Staphylococcus aureus (S. aureus) is a leading cause of bacteraemia and infective endocarditis worldwide, posing significant public health challenges in resource-limited low- and middle-income countries (LMICs). However, whether specific genomic factors influence the development of S. aureus infective endocarditis (SAIE) during S. aureus bacteraemia (SAB) remains unclear. Thus, the study aimed to determine whether clinical SAIE isolates were genomically distinguishable from SAB isolates originating from public hospitals in Gauteng, South Africa. Seventy-seven (54 SAB, 23 SAIE) bloodstream isolates were characterised to assess antimicrobial susceptibility (VITEK®2 system), biofilm formation (crystal violet assay), virulence genes (multiplex-polymerase chain reactions) and genetic relatedness (pulsed-field gel electrophoresis), while 12 representative isolates underwent whole-genome sequencing. A higher SAIE (29.9%) prevalence than previously reported in South Africa was observed, with cases linked to young male persons who inject drugs (P < 0.01). While the SAB and SAIE groups did not differ in virulence profiles, SAB isolates demonstrated higher resistance rates to gentamicin and clindamycin than SAIE isolates (P < 0.05). The endemic Panton-Valentine leukocidin-positive sequence type (ST) 152, clonal complex (CC) 152 lineage predominated in SAIE isolates, while the pandemic CC8, encompassing ST239 and ST612, was exclusive to SAB isolates. Overall, SAB and SAIE isolates were not clearly distinguished by the markers assessed, suggesting that SAIE development may reflect the combined effects of bacterial traits, host susceptibility and exposure-related risk factors, rather than a distinct SAIE-specific genomic profile. These findings highlight the need for continued genomic surveillance of circulating S. aureus lineages to inform targeted infection-control strategies.