Biochemical studies on mycobacterial proteins involved in the transport of fatty acids
Abstract
Mycobacterium tuberculosis (Mtb), an infectious agent responsible for causing tuberculosis, is a serious health threat to individuals who are immunocompromised and a rise in multi-drug resistant and extremely drug resistant strains labels tuberculosis as an emerging infectious disease. Current drugs and therapies which target Mtb are becoming less effective against the active bacteria and are not effective against the dormant pathogen which causes latent tuberculosis in one-third of the world population. Recent studies have shown that fatty acids from human cells are an energy source for the latent pathogen. However, the means by which fatty acids are transported into the mycobacteria remain unknown. We have identified two Mtb adenosine triphosphate binding-cassette transport proteins that shows amino acid sequence identity with a known fatty acid transporter in another bacterium and designate these proteins as potential mycobacterial fatty acid transport proteins (mFATPs). We have cloned the mFATP genes from the genome of Mtb and expressed the proteins in Escherichia coli cells. In this study, we examine the ability of mFATP1 and mFATP2 to enhance fatty acid transport and affect lipid metabolism in the heterologous host cells. Fatty acid uptake assays using radiolabeled oleic acid show increased uptake into cells with the singular expression of mFATP1 and mFATP2 compared to control cells. Preliminary data suggests that mFATP1 enhances the incorporation of fatty acids into lipids. Expression of mFATP1 also allows for increased growth of E. coli cells. Both mFATP1 and mFATP2 potentially act as antibiotic efflux proteins. Our research on understanding the role of this mycobacterial protein is expected to aid the development of novel antibiotics to treat latent tuberculosis disease and the emerging drug resistant strains of tuberculosis.
Degree
M.S.
Advisors
Daniel, Purdue University.
Subject Area
Microbiology|Biochemistry
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