8% for adjuvant-only controls22Mouse NMRISEA (L48R,Y92A,D70R triple mutant)/Freundss.c.Vaccinated mice challenged with (i.v.) experienced a delayed time to death and decreased excess weight loss, vs. gram-positive, halo-tolerant bacterium readily colonizes pores and skin, various mucosal surfaces, soft cells, and bone, as well as indwelling medical products. Approximately 30% of humans are asymptomatic service providers of strains, harboring genes for antibiotic-resistance, staphylococcal enterotoxins (SEs), and additional virulence factors.4 Within the noninstitutionalized populace of the US, Caucasian males less than 65 years old and possessing minimal education are those most likely colonized by (MRSA).4 In addition to the SEs that stimulate specific subsets DDPAC of T cells,2,5 also possesses many other virulence factors that include adhesins, collagenases, protein A, coagulases, hemolysins, and leukocidins.2,3,6 Clearly, the bacterium is very adept at surviving in/on a host via a hefty, diverse arsenal. Often pointed out in popular and medical literature is an ever-increasing resistance of toward antibiotics like methicillin and now vancomycin, which represents a serious societal concern for both humans and animals.7,8 In private hospitals and nursing homes, antibiotic-resistant strains are a particularly deadly bane. Strict adherence to illness control plans is necessary to check inadvertent spread of among staff and individuals. Indeed, is an important health and economic concern throughout the world.9 From a biodefense perspective spanning decades of research, SEB is considered a Category B select agent TPA 023 by the Centers for Disease Control and Prevention that is harmful following inhalation.10,11 When naturally derived by ingestion, the SEs (ACU, and counting) are associated TPA 023 with one of the most prevalent forms of food poisoning found throughout the world.2,12 It is evident that various populations are naturally exposed to these toxins, as demonstrated by SEB seroconversion rates in humans.13 Whether toxin-specific antibodies are developed after ingesting contaminated food, and/or colonization of humans by a toxin-producing strain of growth, and pending strain, release of one (or more) SEs into the tainted food. Only microgram quantities of consumed toxin are TPA 023 needed to cause emesis and diarrhea within approximately 4 h, and one may still experience a general malaise 24 to 72 h later.14 As food poisoning by SEs is non-fatal and of short duration, supportive care is indicated and includes over-the-counter medication for symptomatic relief of gastrointestinal discomfort. Little effort is usually devoted toward developing countermeasures of foodborne illness induced by SEs. Poisoning by the SEs via many different food types is usually rarely fatal for healthy individuals, and occurs around the world; however, the very young and old represent higher risk groups.15 Furthermore, recent murine studies suggest that low, chronic levels of SEB can also experimentally induce autoimmunity.16 This brings up an interesting, yet largely unexplored, aspect of health effects upon humans following chronic colonization by toxin-producing neurotoxin A, another bacterial protein that is of high concern within the biodefense community.31 Superantigen, a term used often in this review, commonly describes the SEs, TSST-1 and structurally related streptococcal pyrogenic exotoxins (SPEs) of that form distinct homology groups based upon amino acid sequence.2,5 There are more than 20 SE variants described in the literature. Furthermore, there are approximately ten SE-like (SEL) proteins produced by that lack emetic properties or have not been tested to date.35 Among the different SE serotypes originally described decades ago, SEA, SED, and SEE share the highest amino acid sequence homology ranging from 53% to 81%. SEB is usually 50C66% homologous with SECs (1, 2, and 3 subtypes).2,5 Despite varying sequences, structural studies, and X-ray crystallography of SEA, SEB, SEC2, and TSST-1 reveal quite conserved conformations with two tightly-packed domains containing -sheet plus -helix structures separated by a shallow groove.36,37 Structure-function studies with site-directed mutagenesis and overlapping peptides of these toxins, along with crystallographic analysis of toxinCMHC II complexes, provide further clues regarding specific residues critical for binding to MHC II and TCR.26,38,39 The SEs and TSST-1 additionally share similar structures (i.e., epitopes) as.