title: Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppression.
abstract: Infectious diseases caused by Staphylococcus aureus present a significant clinical and public health problem. S. aureus causes some of the most severe hospital-associated and community-acquired illnesses. Specifically, it is the leading cause of infective endocarditis and osteomyelitis, and the second leading cause of sepsis in the USA. While pathogenesis of S. aureus infections is at the center of current research, many questions remain about the mechanisms underlying staphylococcal toxic shock syndrome (TSS) and associated adaptive immune suppression. Both conditions are mediated by staphylococcal superantigens (SAgs)-secreted staphylococcal toxins that are major S. aureus virulence factors. Toxic shock syndrome toxin-1 (TSST-1) is the SAg responsible for almost all menstrual TSS cases in the USA. TSST-1, staphylococcal enterotoxin B and C are also responsible for most cases of non-menstrual TSS. While SAgs mediate all of the hallmark features of TSS, such as fever, rash, hypotension, and multi-organ dysfunction, they are also capable of enhancing the toxic effects of endogenous endotoxin. This interaction appears to be critical in mediating the severity of TSS and related mortality. In addition, interaction between SAgs and the host immune system has been recognized to result in a unique form of adaptive immune suppression, contributing to poor outcomes of S. aureus infections. Utilizing rabbit models of S. aureus infective endocarditis, pneumonia and sepsis, and molecular genetics techniques, we aim to elucidate the mechanisms of SAg and endotoxin synergism in the pathogenesis of TSS, and examine the cellular and molecular mechanisms underlying SAg-mediated immune dysfunction.
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, 51 Newton Road, Iowa City, IA, 52242, USA.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kulhankova
authors.forename: Jessica
authors.initials: J
authors.lastname: King
authors.forename: Wilmara
authors.initials: W
authors.lastname: Salgado-Pabón
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D011173:Portraits as Topic; D011817:Rabbits; D012772:Shock, Septic / Q000276:immunology* / Q000473:pathology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D018089:Superantigens / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal