Keywords

Staphylococcus aureus, autolysin, host immune response, human in vivo nasal colonization study, atl

Abstract

Staphylococcus aureus (SA) is a major human pathogen that colonizes the anterior nares in 30% of the human population. Though nasal carriage of SA is a known risk factor for the subsequent spread of SA infections, the dynamics of SA nasal colonization is poorly understood. Our research focuses on understanding the host and bacterial factors that might contribute to the human nasal colonization by SA. In an attempt to elucidate the host response to SA, we performed an autologous human in vivo nasal colonization study, which showed decreased survival rates of SA in hosts who elicited a robust immune response. We also identified a significant correlation between SA nasal colonization and the expression of host proinflammatory, chemotactic and growth factors. Additionally, we functionally disrupted a major autolysin, atl a surface expressed bacterial protein that plays multiple roles in cell separation, adhesion and biofilm formation of SA. Microscopic analysis of the ∆atl strains showed phenotypic differences, including cell clumping and cluster formation due to defective cell separation, which confirmed the functional loss of atl. Subsequent analysis of the ∆atl and wild-type strains revealed that there was no significant difference in their ability to adhere to human nasal epithelial cells (hNEC) in an ex vivo hNEC model. Similarly, our competitive in vivo human nasal colonization study, in which equal colony-forming units of each wild-type and ∆atl SA strain were inoculated in the anterior nares of donors, showed similar survival rates between wild-type and ∆atl. These results suggest that Atl might not be directly involved in the adherence and colonization of SA to the anterior nares. Furthermore, our study suggests that host factors might play a predominant role in determining SA colonization to human anterior nares.

Notes

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Graduation Date

2013

Semester

Fall

Advisor

Cole, Alexander

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Molecular Biology and Microbiology

Degree Program

Biotechnology

Format

application/pdf

Identifier

CFE0005393

URL

http://purl.fcla.edu/fcla/etd/CFE0005393

Language

English

Release Date

June 2019

Length of Campus-only Access

5 years

Access Status

Masters Thesis (Open Access)

Subjects

Dissertations, Academic -- Medicine, Medicine -- Dissertations, Academic

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