Rv1075c of Mycobacterium tuberculosis is a GDSL-Like Esterase and is Important for Intracellular Survival.

Authors:
Dong Yang
Dong Yang
Asan Medical Center
South Korea
Xiaoping He
Xiaoping He
Mayo Clinic College of Medicine
United States
Shaoji Li
Shaoji Li
Ghent University
Belgium
Jiawang Liu
Jiawang Liu
College of Pharmaceutical Sciences
China
Jennifer Stabenow
Jennifer Stabenow
The University of Tennessee Health Science Center
United States
Lillian Zalduondo
Lillian Zalduondo
The University of Tennessee Health Science Center
United States
Stephen White
Stephen White
University of California
United States
Ying Kong
Ying Kong
Beijing Tongren Hospital
China

J Infect Dis 2019 Apr 18. Epub 2019 Apr 18.

Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN.

Mycobacterium tuberculosis (Mtb) lipid metabolism pathways facilitate access to carbon and energy sources for Mtb during infection. A Mtb gene, Rv1075c, was annotated as a conserved hypothetical protein. We have identified that Rv1075c amino acid sequence shares similarities to other bacterial lipase/esterases. With the overexpressed and purified rRv1075c protein, we demonstrated that it had an esterase activity, and preferred short-chain fatty acids, with the highest activity on acetate. Its activity was the highest at 45 °C and pH=9. Site-direct mutagenesis revealed its activity triad as Ser80, Asp244, and His247. We further determined that rRv1075c hydrolyzed triacetin and tributyrin, and the Rv1075c protein was mainly distributed in cell wall and cell membrane of Mtb. Its transcriptional expression was induced at pH=4.5, a condition mimicking the acidic phagosome of macrophage. The mutation of Rv1075c led to significantly reduced bacterial growth in THP-1 cells and human peripheral blood mononuclear derived macrophages, and attenuated Mtb infection in mice (with ~7-fold bacterial load reduction in mouse lungs). Our data suggest that Rv1075c is likely involved in ester and fatty acid metabolism to help Mtb utilize carbon and energy while Mtb stays inside of host cells.

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http://dx.doi.org/10.1093/infdis/jiz169DOI Listing
April 2019
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