Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Heinrichs, David E.

Abstract

Staphylococcus aureus is a resourceful Gram-positive pathogen that is a leading cause of disease worldwide. To cause infections, S. aureus uses a range of virulence factors including fibronectin binding protein A (FnbA). FnbA aids in invasion of host cells and S. aureus overexpressing FnbA was previously shown to be hypervirulent in a murine model of systemic infection. Indeed, FnbA overexpression increased the bacterial burden in visceral organs, as compared to WT-infected mice, as early as 1 hour post-infection. Moreover, heterologous non-pathogenic Staphylococci overexpressing FnbA better colonize murine organs during early infection. I have shown that FnbA overexpression permits an increased number of bacterial foci throughout infected organs, however, this alone is not sufficient for the hypervirulent phenotype due to FnbA overexpression. These findings shed further light on the mechanisms for FnbA-mediated hypervirulence and display the need for coordination between multiple S. aureus virulence factors to cause disease.

Summary for Lay Audience

Staphylococcus aureus is a common pathogen known to cause a variety of diseases ranging from mild skin and soft tissue infections to serious heart, lung, and/or blood infections. The bacterium can do so because it encodes several virulence factors that can evade the immune system, invade host cells, and cause tissue destruction. It was previously shown that the overexpression of a virulence factor, fibronectin binding protein A (FnbA), causes the bacteria to be more lethal during systemic infections. Indeed, the overexpression of FnbA allows the bacteria to better colonize the body, seeding organs in numerous bacterial focal points. The overexpression of FnbA in a non-pathogenic bacterial species shows that FnbA is sufficient for increased colonization, but not lethality seen in FnbA-overexpressing S. aureus. These findings attempt to explain the mechanism for FnbA-mediated hypervirulence by displaying the increase in organ colonization that occurs when FnbA is overexpressed in bacteria during the systemic murine infection model. Overall, this research provides insight on the role of FnbA for dissemination of S. aureus in vivo and highlights the importance for understanding the synergistic interaction of S. aureus virulence factors.

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