Genomic analysis reveals limited pathogen-specific factors for Staphylococcus aureus translocation from blood-to-urine in patients with bacteremia: a cross-sectional study.

OBJECTIVES

Up to 40% of patients with a Staphylococcus aureus bacteremia (SAB) have concomitant asymptomatic S. aureus bacteriuria (SABU). It remains unclear whether pathogen-related mechanisms contribute to SABU secondary to SAB. We compared genomic characteristics of S. aureus from SAB patients with and without SABU.

METHODS

In this cross-sectional study (2020-2023) SAB patients were screened for SABU. Genetic relatedness between blood and urine isolates was assessed by core genome multilocus sequence typing (cgMLST). Genomes were screened for virulence factors, and associations with SABU were analyzed. Pangenome-based and k-mer-based genome-wide association studies (GWAS) were performed.

RESULTS

Among 116 patients (median age: 66.8 years, 44 females), 32 (27.6%) had SABU. All paired blood and urine isolates were genetically identical or differed by ≤6 cgMLST alleles. The presence of set23 (encoding superantigen-like protein SSL8) was associated with SABU (univariate analysis), whereas sec independently predicted absence of SABU (multivariate analysis). Although pangenome-based GWAS identified 141 loci significantly associated with SABU (naïve P-value <0.05), none remained significant after correction for multiple testing. No significant associations were identified in k-mer-based GWAS.

CONCLUSION

Blood and urine isolates were genetically highly related, supporting hematogenous blood-to-urine translocation. Comprehensive genomic analyses provided minimal evidence for pathogen-specific drivers of SABU, suggesting host factors are more important.