Staphylococcal and Streptococcal Superantigens: In Vitro and In Vivo Assays

Staphylococcus aureus and Streptococcus pyogenes represent ubiquitous, formidable pathogens linked to many human and animal diseases [1-3]. These facultative, β-hemolytic bacteria readily colonize skin and various mucosal surfaces through numerous virulence factors that facilitate their survival and dissemination. In addition to the staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin-1 (TSST-1) that interact with specic subsets of T cells [4-6], S. aureus also produces protein A, coagulases, hemolysins, and leukocidins [7,8]. A sobering societal reality involves the ever-increasing resistance of S. aureus toward antibiotics like methicillin [9], and now vancomycin which still represents our major last line of antibiotic defense [10,11]. It is estimated that ~50 million dollars are spent annually in Canada for managing antibiotic-resistant S. aureus in hospitals, and costs for the dairy

17.1 Introduction .................................................................................................. 357 17.2 Physical Characteristics of SEs, TSST-1, and SPEs ..................................... 359 17.3 Binding of SEs, TSST-1, and SPEs to MHC Class II and TCR ...................360 17.4 Cellular Responses to SEs, TSST-1, and SPEs ............................................. 361 17.5 In Vivo Effects of SEs, TSST-1, and SPEs .................................................... 363

17.5.1 Nonhuman Primates: The Historical “Gold Standard” Animal Model ................................................................................... 363 17.5.2 Mice: Not Perfect but Often the Preferred Model ............................ 365 17.5.3 Rabbit Models ................................................................................... 370 17.5.4 Ferret and Shrew Models .................................................................. 370

17.6 Therapeutics and Vaccines Against SEs, TSST-1, and SPEs ....................... 370 17.6.1 Efcacy Studies: Characterized Animal Models are Essential ........ 372

17.7 Conclusions ................................................................................................... 375 References .............................................................................................................. 375

industry are even higher [12]. Indeed, S. aureus represents an important health and economic concern throughout the world [13-16].