Date of Award

Summer 8-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Committee Chair

Mohamed O. Elasri

Committee Chair Department

Biological Sciences

Committee Member 2

Vijay Rangachari

Committee Member 2 Department

Biological Sciences

Committee Member 3

Gordon C. Cannon

Committee Member 3 Department

Biological Sciences

Committee Member 4

Timothy McLean

Committee Member 4 Department

Biological Sciences

Committee Member 5

Glenmore Shearer Jr.

Committee Member 5 Department

Biological Sciences

Abstract

Opportunistic pathogens like Staphylococcus aureus on entering the host can stay colonized at the foci of infection or evade the immune system to disseminate to other sites. In this study we investigated the regulatory influence of the modulator of sarA (msa) on immune evasion and host persistence, employing the hospital-acquired strain S. aureus UAMS-1 and community-acquired strain S. aureus USA300 LAC. In the murine sepsis model, mutation of the msa gene in LAC showed no change in dissemination of infection; however, in UAMS-1 a decrease in microbial load was observed in the lungs. Differential regulation by the msa gene was also observed in the blood survival and neutrophil assays. Several evasion factors were found to be regulated by msa, namely the scn, clfA, spa, aur, and sak genes. Interestingly, the combination of factors and the regulation of these factors differed in the two strains.

S. aureus form biofilms on post-surgical wounds, prosthetic devices, and various host tissues that are resilient to immunological clearance and antimicrobial treatments. Biofilm detachment is a stage of biofilm development that aids in metastasis of infection. Proteases are one of the factors that trigger biofilm detachment. In our study, we observed msa to regulate proteases of S. aureus strain LAC when they are not in the form of a biofilm community; however, when they form biofilms the regulatory effect on proteases by the msa gene is absent. Thus, we show the environment-dependent behavior of the msa gene.

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