AUTHOR=Spaulding Adam R., Satterwhite Erin A., Lin Ying-Chi , Chuang-Smith Olivia N., Frank Kristi L., Merriman Joseph A., Schaefers Matthew M., Yarwood Jeremy M., Peterson Marnie L., Schlievert Patrick M. TITLE=Comparison of Staphylococcus aureus strains for ability to cause infective endocarditis and lethal sepsis in rabbits JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=2 YEAR=2012 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2012.00018 DOI=10.3389/fcimb.2012.00018 ISSN=2235-2988 ABSTRACT=

Staphylococcus aureus is a major cause of infective endocarditis (IE) and sepsis. Both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains cause these illnesses. Common S. aureus strains include pulsed-field gel electrophoresis (PFGE) types USA200, 300, and 400 types where we hypothesize that secreted virulence factors contribute to both IE and sepsis. Rabbit cardiac physiology is considered similar to humans, and rabbits exhibit susceptibility to S. aureus superantigens (SAgs) and cytolysins. As such, rabbits are an excellent model for studying IE and sepsis, which over the course of four days develop IE vegetations and/or fatal septicemia. We examined the ability of MRSA and MSSA strains (4 USA200, 2 USA300, 2 USA400, and three additional common strains, FRI1169, Newman, and COL) to cause vegetations and lethal sepsis in rabbits. USA200, TSST-1+ strains that produce only low amounts of α-toxin, exhibited modest LD50 in sepsis (1 × 108 – 5 × 108) colony-forming units (CFUs), and 3/4 caused significant IE. USA200 strain MNPE, which produces high-levels of α-toxin, was both highly lethal (LD50 5 × 106 CFUs) and effective in causing IE. In contrast, USA300 strains were highly effective in causing lethal sepsis (LD50s 1 × 106 and 5 × 107 CFUs) but were minimally capable of causing IE. Strain Newman, which is phylogenetically related to USA300 strains, was not highly lethal (LD50 of 2 × 109 CFUs) and was effective in causing IE. USA400 strains were both highly lethal (LD50s of 1 × 107 and 5 × 107 CFUs) and highly effective causes of IE. The menstrual TSS isolate FRI1169, that is TSST-1+, produces high-levels of α-toxin, but is not USA200, was both highly lethal and effective in causing IE. Additional studies showed that phenol soluble modulins (PSMs) produced by FRI1169 were important for sepsis but did not contribute to IE. Our studies show that these clonal groups of S. aureus differ in abilities to cause IE and lethal sepsis and suggest that secreted virulence factors, including SAgs and cytolysins, account for some of these differences.