Genomic comparison between staphylococcus aureus isolates from patients with bacteraemia and infective endocarditis from public hospitals in Gauteng

Abstract

Staphylococcus aureus (S. aureus) is a leading cause of bacteraemia (SAB) and infective endocarditis (IE) globally. In South Africa, S. aureus IE (SAIE) poses significant public health challenges among vulnerable populations, such as the immunocompromised and persons who inject drugs (PWIDs). However, data on SAIE in South African settings is limited and whether specific genomic virulence determinants drive SAIE outcomes remains unclear.

The study examined phenotypic and genotypic profiles of 77 S. aureus bloodstream (54 SAB and 23 SAIE) isolates collected from a public health diagnostic laboratory serving multiple public hospitals across Gauteng to determine whether SAIE isolates are genomically distinct from SAB isolates. Antimicrobial susceptibility testing (AST) data was obtained through VITEK®2 automated systems (BioMérieux, France), multiplex polymerase chain reaction (M-PCR) assays screened for virulence genes, 96-well microtiter plate assays determined biofilm-formation and genetic relatedness was investigated using pulsed-field gel electrophoresis (PFGE) with results guiding the selection of 12 representative isolates for analysis with whole-genome sequencing (WGS).

Staphylococcus aureus IE was significantly associated with: i) male sex (P < 0.001), ii) 25 years to 44 years age group (P = 0.002) and iii) PWIDs status (P < 0.001). Notably, where AST data was available [76/77 (53 SAB and 23 SAIE)], the SAB group demonstrated significantly higher antimicrobial resistance (AMR) rates to gentamicin and clindamycin, with 18.9% (10/53) and 20.8% (11/53), respectively, compared to 0% in SAIE (P < 0.05). All isolates (76/76) remained susceptible to linezolid, teicoplanin and vancomycin. Most isolates [55.8% (43/77)] harboured 10 or more of the 20 screened virulence genes, with adhesion- and exoenzyme-associated genes most prevalent. Toxins were uncommon; however, the Panton-Valentine leukocidin (PVL) gene was detected in 35.1% (27/77) of isolates. Strong biofilm formation predominated in both SAB [33.3% (18/54)] and SAIE [52.2% (12/23)] isolates, with no significant differences in biofilm or virulence profiles between infection types (P > 0.05).

Genetic diversity was apparent and WGS revealed widespread AMR, virulence and mobile genetic elements across sequence types (STs), largely supporting the findings of the AST, M-PCR and PFGE assays used in this study. Several SAB and SAIE isolates exhibited high genetic similarity, suggesting the circulation of highly pathogenic strains within the study setting, particularly among PWID populations. Eight STs across seven clonal complexes (CCs) were identified, with 58.3% (7/12) of isolates belonging to CC152 or CC8. The endemic PVL-positive ST152/CC152 lineage predominated in representative SAIE isolates [50% (3/6)], while the pandemic CC8, encompassing ST239, ST508 and ST612, was exclusive to SAB isolates ([50% (3/6)]).

No distinct virulence markers exclusively associated with SAIE were identified, suggesting that all SAB isolates may have the potential to progress to SAIE. While pathogenic traits of S. aureus are important; host factors, particularly in high-risk groups like PWIDs, may be more significant predictors of disease progression. The circulation of diverse S. aureus strains with significant AMR and virulence profiles within public hospitals and potentially community settings underscores the need for proactive surveillance to monitor transmission dynamics and inform targeted infection control strategies.