Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

Abstract

Infective endocarditis (IE)((1)) is a severe condition complicating 10-25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)((2)). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia.

Pathogenic Characteristics of Staphylococcus aureus Endovascular Infection Isolates from Different Clonal Complexes

“…This agrees with previous studies that also reported significant attenuation of virulence for CC30 in both the G. mellonella and murine sepsis models (Sharma-Kuinkel et al, 2015). Remarkably, our results indicate high virulence for strains of CC15, with substantial larvae mortality in the first 48 h. Although it has been associated with increased severity of infection and infective endocarditis, there is limited information about the pathogenic mechanisms of CC15 and its involvement in endovascular complications (Fowler et al, 2007; Bouchiat et al, 2015). In agreement with previous reports, we found that strains with a functional agr , associated with an up-regulated production of toxins and secreted virulence factors, were significantly more virulent than strains with a dysfunctional agr regulator (Peleg et al, 2009).…”

“…Moreover, previous reports seem to indicate that no single virulence factor alone is sufficient to describe S. aureus endovascular pathogenesis and a cumulative effect from different factors probably offers the most realistic scenario (Peacock et al, 2002; Bouchiat et al, 2015). S. aureus has a highly clonal population structure with CCs comprising closely related, although not identical, genetic backgrounds (Lindsay et al, 2006; Dayan et al, 2016).…”

“…Therefore, the analysis of the pathogenic characteristics of representative S. aureus genetic clonal complexes seems an appropriate means by which further our understanding of the etiology of this disease. Indeed, previous studies showed that, although most S. aureus genotypes exhibit the capacity to cause invasive disease, bacteremia caused by strains belonging to particular clonal complexes (CC5, CC15, and CC30) has been associated with endovascular complications (Fowler et al, 2007; Nienaber et al, 2011; Bouchiat et al, 2015). Methicillin resistance has also been linked to an increased risk for the development of hematogenous complications (Fowler et al, 2005, 2007).…”

Necrotizing Soft Tissue Infections Staphylococcus aureus - but not Streptococcus pyogenes-isolates display high rate of internalization and cytotoxicity toward human myoblasts

“…It is based on, but not restricted to, findings of necrosis, dissolved or deliquescent soft tissue, and fascial and muscular affection (22). The invasive non-NSTI SA control strains consisted in Bloodstream infection (BSI) strains (12 infective endocarditis, 9 bacteremia without infective endocarditis) collected during a prospective cohort study on S. aureus bacteremia (VIRSTA) (23). Those strains were chosen in order to genotypically match NSTI strains on the basis of micro-array-deduced clonal complexes (23) confirmed by whole genome sequencing (Illumina MiSeq technology, Illumina, San Diego, USA, with 16-266 x coverage, median 137).…”

NorK, a novel norfloxacin efflux pump in Staphylococcus aureus

“…Together these data suggest that NorK belongs to the same family as the Nor proteins previously described. To assess if this pump was widely distributed among S. aureus , BLAST analysis on a large collection of genotypically diverse bacteremia isolates (9) was performed. The results showed that 98% (123/126) harbor norK genes (identity and coverage >90%).…”