Semester of Graduation

Summer 2025

Degree

Master of Science (MS)

Department

Department of Biological sciences

Document Type

Thesis

Abstract

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that produces numerous immune evasion molecules that target various components of the host immune defense to cause infection. One of these is a family of virulence factors, Staphylococcal superantigen-like proteins (SSLs) with 14 members that exhibit host immune-evasion functions. SSL11 has been reported to inhibit neutrophil migration, preventing its recruitment to sites of infection. However, its role in vivo and effect on neutrophil phagocytosis have not been known. This thesis focuses on studying the effect of recombinant SSL11 protein in an in vivo S. aureus-induced pneumonia model and in vitro neutrophil phagocytosis. We hypothesize that SSL11 protein (SSL11/WT) reduces excessive inflammation by impairing neutrophil migration, thus offering protection during severe S. aureus-induced pneumonia from the damage caused by excess neutrophil, whereas mutated SSL11 (SSL11/RA), lacking the SLeX binding site required for leukocyte migration inhibition, will not have similar protection. Mice were infected with S. aureus (SA) by oropharyngeal aspiration with treatment of SSL11/WT or SSL11/RA. Co-treatment of SSL11/WT and S. aureus inoculum resulted in a greater bacterial load in the lungs compared to the control group with only S. aureus infection. In contrast, pretreatment of SSL11/WT before infection led to a reduction in S. aureus in the lungs of female mice at 24 and 48 hours. Bronchoalveolar lavage fluid (BALF) analysis in the SSL11/WT pretreatment group in female mice shows a pattern of decreased neutrophil, monocyte, and macrophage counts with reduced cytokine release of IL-6 and MCP-1. Assessment of neutrophil-mediated phagocytosis of S. aureus treated with SSL11 protein shows that all SSL11/WT and SSL11/RA treatment significantly lowers the S. aureus phagocytosis and killing inside the phagolysosome by neutrophil in an SLeX-independent manner. These results suggest SSL11/WT pretreatment has a pattern of decreased neutrophil recruitment to the site of infection but somehow enhances bacterial clearance in the lungs post-24 hours in female mice. Meanwhile, both forms of SSL11 decrease the phagocytosis by the neutrophils in vitro, which is beneficial for S. aureus as it facilitates its survival. Further study on the topic might provide a new target against S. aureus infections.

Date

7-14-2025

Committee Chair

Chen, Chen

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