Doctoral Dissertations

Date of Award

8-2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Elizabeth Fozo

Committee Members

Todd Reynolds, Gladys Alexandre, Erik Zinser

Abstract

Enterococcus faecalis is a commensal of the mammalian intestine and an opportunistic pathogen that infects various locations in the human host. Specifically, the organism can infect surgical wounds, the urinary tract, and is an agent of endocarditis. Regardless of niche, this organism has access to fatty acid sources in the host, which may influence its ability to survive and cause infection; yet, the effects of exogenous fatty acids were unknown in E. faecalis. We have shown that complex sources of fatty acids such as bile or serum can significantly alter the membrane content and protect E. faecalis from acute membrane damage. Experiments with individual bile and serum components revealed that protection from acute membrane stress could be attributed to unsaturated fatty acids found within these host fluids.

To better discern how complex sources of fatty acids such as bile or serum could impact growth and physiology of E. faecalis so dramatically, we decided to examine the effects of individual fatty acids on cellular physiology. To date, virtually no studies had examined the role of fatty acids on E. faecalis. We concluded that unsaturated fatty acids are necessary for growth and could support growth in the absence of de novo fatty acid biosynthesis. Saturated fatty acids were shown to be toxic to E. faecalis, distorting cell morphology and impeding growth.

The significance of unsaturated fatty acids is evident as even small amounts could rescue cells from toxic fatty acids. These data help clarify why bile and serum, which contain a mixture of unsaturated and saturated fatty acids, are not toxic. Our experiments show not only that E. faecalis has a requirement for unsaturated fatty acids, but also that growth can be supported entirely with unsaturated fatty acids. Moreover, toxicity caused by fatty acids is primarily attributed to saturation and length. In conclusion, exogenous fatty acids have tremendous impacts on cell physiology and stress survival; furthermore, understanding these is critical for developing effective therapeutics.

Comments

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