Date of Award

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

Staphylococcus aureus is an important and dangerous human and animal pathogen that causes a wide variety of diseases. The organism is a significant cause of nosocomial infections, as well as community-associated diseases due to a combination of toxin-mediated virulence, invasiveness, and antibiotic resistance. Resistance to multiple antibiotics, particularly to penicillin and methicillin, is common in S. aureus and makes treatment especially difficult. Recently, the current threat from this pathogen is the pandemic spread of community associated methicillin-resistant S. aureus (CA-MRSA) which have become the most frequent causes of skin and soft-tissue infections in the community and are replacing traditional hospital associated methicillin-resistant S. aureus (HA-MRSA) on a large scale. The pathogenesis of CA-MRSA infections is a complex process involving a diverse array of secreted and surface-associated virulence determinants that are coordinately expressed at different stages of infection. Among the secreted factors is a large family of superantigen exotoxins. Superantigens induce skin inflammatory responses in atopic dermatitis, which is commonly associated with S. aureus infection. Staphylococcal superantigens include staphylococcal enterotoxins, classically the common causes of food poisoning, nonmenstrual toxic shock syndrome (TSS), and toxic shock syndrome toxin 1 (TSST-1), the cause of both menstrual and nonmenstrual TSS. Many genes from S. aureus make putative proteins which have high homology with known S. aureus superantigens. The aim of this study is to identify and characterize a potential superantigen that has high homology with known S. aureus exotoxins. This study focuses on a unique gene that encodes an exported protein, SAS0347, found on the chromosome of the CA strain methicillin-sensitive S. aureus MSSA476. The protein SAS0347 was chosen because it has high homology to proteins identified in other S. aureus strains known for superantigenicity. The goal of this work is to characterize SAS0347 and determine whether it has superantigenicity. The gene of interest has been successfully cloned, expressed, and proliferation assays performed with treated mouse splenocytes and T-cells in vitro and in vivo. The proliferation assays demonstrated that SAS0347 has a similar proliferative profile as the positive control staphylococcal enterotoxin B (SEB).

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