Abstract 10206: First in-vivo Evidence of Aureolysin ( aur ) Up-Regulation by Staphylococcus Aureus Causing Invasive Prosthetic Valve Endocarditis

Abstract

Background: Staphylococcus aureus prosthetic valve endocarditis (PVE) is resistant to antimicrobial therapy and commonly associated with tissue invasion, which necessitates complex high risk surgical intervention for cure. Hypothesis: S. aureus virulence in infective endocarditis (IE) is dynamic and changes upon colonizing cardiac valves from blood stream. Methods: Six patients undergoing cardiac surgery for left-sided S. aureus IE, 3 native (NVE) and 3 PVE, were included in this study. Vegetation samples were collected during surgery as well as corresponding blood culture isolates during S. aureus bacteremia. Total RNA was extracted from all samples and underwent mRNA sequencing for transcriptomic analysis of S. aureus . Data was pooled into STAR aligner and gene expression related to virulence factors was compared between different groups (Deseq2; p-value < 0.05 for statistical significance). Results: In NVE vegetations, S. aureus showed an increased expression of genes associated with biofilm formation, cell division, and metabolic activity, when compared to blood culture isolates (e.g. rsmA , agrB , dnaK , clpB , ezrA , fusA , ftsZ , adh , pstS , qoxA ). S. aureus isolated from blood cultures had significantly higher expression of clfA (encoding for clumping factor A) compared to cardiac vegetations. Interestingly, in PVE vegetations, S. aureus had a significant higher expression of aur (encoding for metalloprotease aureolysin) compared to corresponding blood culture isolates or NVE vegetations. Aureolysin is an important virulence factor responsible for immune evasion and toxin production. Conclusions: In clinical IE, S. aureus up-regulates genes responsible for biofilm formation when attached to cardiac valves. Planktonic S. aureus cells in the blood stream express clfA , which could bind to fibrinogen to clump within platelet network to form vegetations. On prosthetic valves, S. aureus expresses aureolysin, which could function to evade the host immune response and promote destruction of cardiac tissues. These novel in-vivo findings provide explanations for S. aureus IE pathophysiology that warrant further investigation.