Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds critical insight into host lipid utilization by M. tuberculosis.

The Journal of Biological Chemistry
Khundrakpam Herojit SinghBichitra Kumar Biswal

Abstract

Mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. To survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. For example, M. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. M. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for cleavage of fatty acids from host lipids? We show herein that a previously uncharacterized membrane-associated M. tuberculosis protein encoded by Rv2672 is conserved exclusively in actinomycetes, exhibits both lipase and protease activities, is secreted into macrophages, and catalyzes host lipid hydrolysis. In light of these functions, we annotated Rv2672 as mycobacterial secreted hydrolase 1 (Msh1). Furthermore, we found that this enzyme is up-regulated both in an in vitro model of hypoxic stress and in a mouse model of M. tuberculosis infection, suggesting that the pathogen requires Msh1 under hypoxic conditions. Silencing Msh1 expression compromised the ability of M. tuberculosis to prol...Continue Reading

References

Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·D HirschH F Lodish
Nov 13, 1998·The Journal of Biological Chemistry·D J FalconeL Fernandes
Sep 7, 2001·Annual Review of Microbiology·L G Wayne, C D Sohaskey
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Mar 2, 2005·Trends in Microbiology·JoAnne L Flynn, John Chan
Dec 20, 2005·The Journal of Pathology·Timo Ulrichs, Stefan H E Kaufmann
Jul 15, 2006·Journal of Microbiological Methods·Mandana RezwanMamadou Daffé
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Mar 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Amit K Pandey, Christopher M Sassetti
Jun 2, 2009·Nature Reviews. Microbiology·Noel H SmithStephen V Gordon
Aug 21, 2009·Nature Immunology·David G RussellFrédéric Altare
Jan 28, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mathieu SchuéStéphane Canaan
Jul 20, 2010·Cell Host & Microbe·David G RussellKyle H Rohde
Jun 2, 2011·PLoS Biology·Seung-Hun BaekChristopher M Sassetti
Oct 1, 2011·Nature Methods·Thomas Nordahl PetersenHenrik Nielsen
Jan 12, 2013·The Journal of Biological Chemistry·Wonsik LeeDavid G Russell
Oct 18, 2013·Molecular Biology and Evolution·Koichiro TamuraSudhir Kumar
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Apr 2, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Quanju ZhaoJianping Xie
Nov 22, 2014·Nucleic Acids Research·Aron Marchler-BauerStephen H Bryant
Feb 26, 2015·Nature Communications·Eira ChoudharyNisheeth Agarwal
Mar 15, 2015·Enzyme and Microbial Technology·Jin GuoXiao-Jun Huang
Apr 18, 2015·Nucleic Acids Research·Alexey DrozdetskiyGeoffrey J Barton
Nov 7, 2015·Current Opinion in Microbiology·Rustin R LovewellBrian C VanderVen

❮ Previous
Next ❯

Citations

Jan 19, 2018·Journal of Leukocyte Biology·Michael D StutzMarc Pellegrini
Sep 27, 2018·Future Microbiology·Nagender Rao RameshwaramSangita Mukhopadhyay
Jan 30, 2018·Frontiers in Cellular and Infection Microbiology·Elena Cardenal-MuñozThierry Soldati
Oct 12, 2018·Drug Development Research·Erik M Larsen, R Jeremy Johnson
Jun 30, 2019·Science·Daniel J GreenwoodMaximiliano G Gutierrez
Oct 20, 2018·Frontiers in Cellular and Infection Microbiology·Sudhanshu AbhishekIndu Verma
Aug 16, 2018·Frontiers in Immunology·Benoit AllardJames G Martin
Jan 8, 2021·International Journal of Biological Macromolecules· ShivangiLaxman S Meena
Apr 4, 2021·International Journal of Molecular Sciences·Miriam HetzelNico Lachmann
Dec 14, 2018·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Jan MadackiRoland Brosch
May 27, 2021·FEMS Microbiology Reviews·Ivy MallickStéphane Canaan

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Bacterial Transport Proteins

Bacterial transport proteins facilitate active and passive transport of small molecules and solutes across the bacterial membrane. Here is the latest research.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Bacterial Transport Proteins (ASM)

Bacterial transport proteins facilitate active and passive transport of small molecules and solutes across the bacterial membrane. Here is the latest research.

Related Papers

Journal of Pathogens
Ayssar A ElaminMahavir Singh
The Journal of Laboratory and Clinical Medicine
V L Richmond
Frontiers in Bioscience : a Journal and Virtual Library
Timo Ulrichs, Stefan H E Kaufmann
© 2022 Meta ULC. All rights reserved