Theses and Dissertations
Issuing Body
Mississippi State University
Advisor
Seo, Keun Seok
Committee Member
Pinchuk, Lesya
Committee Member
Pruett, Stephen
Committee Member
Thornton, Justin
Date of Degree
8-7-2020
Original embargo terms
Worldwide
Document Type
Dissertation - Open Access
Major
Veterinary Medical Science
Degree Name
Doctor of Philosophy
College
College of Veterinary Medicine
Department
Veterinary Medical Science Program
Abstract
Staphylococcus aureus employs an array of virulence factors to aid in its pathogenesis. A subset of cytotoxins termed bi-component leucocidins have been characterized as important determinants in the host-pathogen interaction in S. aureus infections. While they have been studied over a century, bi-component leucocidins’ complex mechanisms in pathogenesis have not been fully elucidated. Secreted as monomers, with the exception of LukAB/GH, many combinations of the S- (HlgA, HlgC, LukE, LukS, LukA/H) and F- (HlgB, LukD, LukF, LukB/G) components have demonstrated cell lysis via pore formation and a magnified proinflammatory response at sublytic concentrations. While studies have described various host cellular receptors and therapeutic strategies to evade leucocidin binding, a common receptor for all the leucocidins has yet to be classified. Challenges in data extrapolation have occurred due to non-native protein expression methods and species specificity of the leucocidin components. In turn, developing successful therapeutic strategies has proven problematic with a need for multimodal therapy. Thus, our studies aimed to clarify the bi-component leucocidins’ cytotoxic effects on multiple subsets of leukocytes using a native protein expression system and to identify a novel human leukocyte receptor common to all leucocidins. Overall, combinations with HlgA and LukE demonstrated the highest degrees of cytotoxicity against PMNs and PBMCs. Coronin 1A was discovered as a common receptor for all cognate pairs of bi-component leucocidins, except LukAB/GH. In conclusion, our results have expanded the knowledge of the cellular targets for leucocidin cytotoxicity and have described a common leucocidin receptor as a potential therapeutic target against the bi-component leucocidins.
URI
https://hdl.handle.net/11668/18465
Recommended Citation
Rutter, Jaime, "Characterizing human receptor-mediated cytotoxicity by staphylococcal bi-component leucocidins in S. aureus pathogenesis" (2020). Theses and Dissertations. 1042.
https://scholarsjunction.msstate.edu/td/1042