Abstract

Staphylococcus aureus is one of the major bacterial pathogens responsible for approximately one-third of infective endocarditis globally. For successful infection, S. aureus is largely attributed to its ability to form biofilms and interact with host cells. We hypothesized that serotype-specific S. aureus interactions with cardiac endothelial cells reveal its tropism to cardiac tissue and the spectrum of tissue-specific endocarditis. The study compared the host-pathogen interactions of serotype 5 and serotype 8 of S. aureus at cellular levels, measuring their biofilm-forming capacity on plastic and adhesion to and invasion in murine coronary endothelial cells (MCECs) using standard adhesion and invasion assays. In addition, we also assessed viability of MCECs (e.g., cytotoxicity) and transcytosis of both serotypes after exposure at different time points. Furthermore, the existing whole-genome sequence data of both serotypes were analyzed to find out serotype-specific genes, especially major factors, which are related to and regulate bacterial biomass formation and adhesion to host cells. Serotype 5 S. aureus demonstrated significantly higher biofilm formation capacity compared to serotype 8 S. aureus. Similarly, serotype 5 showed a significantly higher level of adhesion to and invasion in MCECs compared to serotype 8. Interestingly, the intracellular survival capacity of both serotypes was comparable; however, the transcytosis colonies were significantly higher for serotype 8 compared to serotype 5. In addition, the viability of MCECs was significantly decreased after exposure to serotype 5 (at 16 hours post-challenge) compared to serotype 8. Besides, the whole-genome sequence data also revealed that serotype 5 S. aureus carried four distinct major adhesion factors (e.g., fnbB, sdrD, efb, sasK) compared to serotype 8, suggesting its serotype-specific key factors, which might be responsible for the augmentation of bacterial biomass formation, adhesion to, and invasion in host endothelial cells. Overall, we reported that serotype 5 S. aureus demonstrates significantly higher biomass formation and adhesion to, invasion or cytotoxicity to MCECs, which are correlated with the above-mentioned distinct genotypic biomarkers.

Key words: Adhesion, Biofilm formation, Endocarditis, Invasion, Staphylococcus aureus, Transcytosis