Staphylococcus aureus is an opportunistic pathogen causing a wide range of diseases in humans and animals. S. aureus produces numerous exotoxins causing toxin-associated syndromes, surface proteins for colonization and persistence on the host organs and prosthetic devices, numerous enzymes utilized to invade and to destroy host tissues, and antibiotic resistance. Staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin-1 (TSST-1) are the family of superanfigens (SAgs) and are important virulence factors of S. aureus. Although the toxic properties of SAg have been well characterized, this prediction was based on the observations using high concentrations of SAgs. Several lines of evidence in animal models indicated that low concentrations of SAg was produced in chronic S. aureus infection. Furthermore, our results in the animal models demonstrated that a low dose stimulation with SAg induced immunosuppressive regulatory and suppressor T cells and proinflammatory dendritic cells. Also, a deletion of the 9 SAg genes or a vaccination with 9 recombinant SAgs greatly attenuated staphylococcal pathogenesis. These results suggest that SAg plays an important role in staphylocccal pathogenesis. However, parallel knowledge in humans is critically limited. In this proposed study, we will characterize phenotypic and functional characteristics of human T cells and antigen presenting cells stimulated with various concentrations of SAg to elucitate the roles of these cells in the staphylococcal pathogenesis. If successful, this approach will enhance the current understanding of SAg immunopathobiology and allow the development of a novel preventive strategy against diseases associated with SAg. This will be accomplished by completing following three specific aims;
Aim 1 : Determine the dose-dependent effect of SAg stimulation on the phenotypic and functional characteristics of T cells;
Aim 2 : Determine the dose-dependent effect of SAg stimulation on the phenotypic and functional characteristics of APCs;
Aim 3 : Determine cellular signaling pathways and gene expression in response to dose-dependent SAg stimulation.
A cadre of virulece factors and antimicrobial resistence potisions S. aureus as a formidable human and animal pathogens. Superanfigens are major virulece factors of S. aurues. However, the causal relations with staphylococcal infection in humans are poorly understood. Obtaining such knowledge is critically important to develop novel preventive and therapeutic starategies against diseases associated with SAgs.
|Bryant, Joseph C; Dabbs, Ridge C; Oswalt, Katie L et al. (2016) Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release. BMC Microbiol 16:271|
|Wright, Morgan L; Pendarvis, Ken; Nanduri, Bindu et al. (2016) The Effect of Oxygen on Bile Resistance in Listeria monocytogenes. J Proteomics Bioinform 9:107-119|
|Seo, Keun Seok (2016) Monkey Feeding Assay for Testing Emetic Activity of Staphylococcal Enterotoxin. Methods Mol Biol 1396:125-31|
|Park, Joo Youn; Seo, Keun Seok (2016) Quantification of a Selective Expansion of T Cell Receptor VÎ² by Superantigen Using Real-Time PCR. Methods Mol Biol 1396:167-80|
|Alugubelly, Navatha; Hercik, Kamil; Kibler, Peter et al. (2016) Analysis of differentially expressed proteins in Yersinia enterocolitica-infected HeLa cells. Biochim Biophys Acta 1864:562-9|
|Brown, Lindsey R; Gunnell, Steven M; Cassella, Adam N et al. (2016) AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness. PLoS One 11:e0146785|
|Nanduri, Bindu; Shack, Leslie A; Rai, Aswathy N et al. (2016) Use of focused ultrasonication in activity-based profiling of deubiquitinating enzymes in tissue. Anal Biochem 515:9-13|
|Dhital, Saphala; Stokes, John V; Park, Nogi et al. (2016) Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation. Cell Immunol :|
|Moon, Bo Youn; Park, Joo Youn; Robinson, D Ashley et al. (2016) Mobilization of Genomic Islands of Staphylococcus aureus by Temperate Bacteriophage. PLoS One 11:e0151409|
|Ferguson, Lucas; Olivier, Alicia K; Genova, Suzanne et al. (2016) Pathogenesis of Influenza D Virus in Cattle. J Virol 90:5636-42|
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