Potential Influence of Staphylococcus aureus Clonal Complex 30 Genotype and Transcriptome on Hematogenous Infections

Abstract

Abstract Background.  The contemporary Staphylococcus aureus clonal complex (CC) 30 lineage is associated with complicated infections, including endocarditis and osteomyelitis. This lineage diverged from the phage-type 80/81 S aureus clone responsible for a major bacterial epidemic of the 20th century. The genome and transcriptome features that contribute to complicated infections of the CC30 lineage are unknown. Methods.  Twenty-nine clinical methicillin-resistant S aureus (MRSA) strains (8 from CC30 and 21 from other major CCs were evaluated for virulence using murine and Galleria mellonella sepsis models. Genomic features of CC30 were ide.jpegied by comparative genome sequencing and RNA-Seq transcriptome analysis of the 29 strains and 31 previously sequenced S aureus genomes. Results.  The CC30 isolates displayed lower virulence in the sepsis models compared with other CCs [P < .0001]. Comparisons of orthologous proteins and transcriptome analysis ide.jpegied genes (eg, nitric oxide reductase) and changes in metabolic pathways (eg, pyrimidine metabolism) that contribute to the distinct CC30 phenotype. Previously reported nonsynonymous single-nucleotide polymorphisms (SNPs) were found in accessory gene regulator C (agrC) and α-hemolysin (hla), molecules important for virulence. Additional nonsynonymous SNPs conserved across clinical CC30 isolates when compared with the first sequenced contemporary CC30 clone, MRSA-16, were ide.jpegied in multiple genes, suggesting continuing evolutionary divergence in this lineage. Conclusions.  Genomic and transcriptional analyses suggest that the CC30 lineage has acquired metabolic features that contribute to persistent and complicated infections. Absence of sepsis-induced mortality in animal models may be due in part to its unique genomic profile and suggests that specific genotypes of S aureus elicit distinct types of infection types.