Gasch, O. | bioRxiv Science

bioRxiv2025

Comparative mortality of dominant Staphylococcus aureus lineages in human bacteremia and animal infection models

Staphylococcus aureus is a major cause of severe infections including infective endocarditis, but lineage-specific virulence determinants remain unclear. We analyzed 77 S. aureus bacteremic isolates from major lineages using phenotypic assays, infection models, and transcriptomics. Our results revealed significant heterogeneity in S. aureus pathogenicity. ST398 isolates exhibited heightened virulence, characterized by increased hemolysin production, whereas CC30 strains showed reduced growth, biofilm formation, and infectivity. Notably, the ST398 agrC mutant Sau7 exhibited unique phenotypic behavior, with high biofilm production and decreased virulence in Galleria mellonella larvae model. Infection studies in the rabbit experimental endocarditis model showed increased vegetation size and bacterial load in Sau7-infected animals, highlighting the role of agr system in S. aureus colonization and biofilm formation. Transcriptomic analysis identified key pathways, including quorum sensing systems and hemolysins, driving virulence in ST398 strains. These findings provide insights into the lineage-specific virulence mechanisms and the multifaceted nature of S. aureus pathogenicity.

microbiology↗

bioRxiv2023

Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic

Genomic analyses of bacterial isolates are necessary to monitor the prevalence of antibiotic resistance genes and virulence determinants. Herein, we provide a comprehensive genomic description of a collection of 339 Staphylococcus aureus strains isolated from patients with bacteremia between 2014 and 2022. Nosocomial acquisition accounted for 56.6% of episodes, with vascular catheters being the predominant source of infection (31.8%). Cases of fatality (27.4%), persistent bacteremia (19.5%) and diagnosis of septic emboli (24.2%) were documented. During the COVID-19 pandemic, we observed a 140% increase of the episodes of S. aureus bacteremia per year, with a concomitant increase of the cases from nosocomial origin. This prompted us to investigate the existence of genetic features associated with S. aureus isolates from the COVID-19 pandemic. While genes conferring resistance to {beta}-lactams (blaI-blaR-blaZ), macrolides (ermA, ermC, ermT, mphC, msrA) and aminoglycosides (ant(4)-Ia, ant(9)-Ia, aph(3)-IIIa, aph(2)-Ih) were prevalent in our collection, detection of the msrA and mphC genes increased significantly in pandemic S. aureus isolates. Similarly, we observed a higher prevalence of isolates carrying the genes encoding the Clumping Factors A and B, involved in fibrinogen binding. Of note, macrolides were extensively used as accessory therapy for COVID-19 and fibrinogen levels were usually elevated upon SARS-CoV-2 infection. Therefore, our results reveal a remarkable adaptation of the S. aureus isolates to the COVID-19 pandemic context and demonstrates the potential of whole-genome sequencing to conduct molecular epidemiology studies.

genomics↗