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Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis

Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb...

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Autores principales: Nazarova, Evgeniya V, Montague, Christine R, La, Thuy, Wilburn, Kaley M, Sukumar, Neelima, Lee, Wonsik, Caldwell, Shannon, Russell, David G, VanderVen, Brian C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487216/
https://www.ncbi.nlm.nih.gov/pubmed/28708968
http://dx.doi.org/10.7554/eLife.26969
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author Nazarova, Evgeniya V
Montague, Christine R
La, Thuy
Wilburn, Kaley M
Sukumar, Neelima
Lee, Wonsik
Caldwell, Shannon
Russell, David G
VanderVen, Brian C
author_facet Nazarova, Evgeniya V
Montague, Christine R
La, Thuy
Wilburn, Kaley M
Sukumar, Neelima
Lee, Wonsik
Caldwell, Shannon
Russell, David G
VanderVen, Brian C
author_sort Nazarova, Evgeniya V
collection PubMed
description Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability. We also demonstrate that Mce1 functions as a fatty acid transporter in Mtb and determine that facilitating cholesterol and fatty acid import via Rv3723/LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key function for Rv3723/LucA in in coordinating thetransport of both these substrates. DOI: http://dx.doi.org/10.7554/eLife.26969.001
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spelling pubmed-54872162017-06-30 Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis Nazarova, Evgeniya V Montague, Christine R La, Thuy Wilburn, Kaley M Sukumar, Neelima Lee, Wonsik Caldwell, Shannon Russell, David G VanderVen, Brian C eLife Microbiology and Infectious Disease Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability. We also demonstrate that Mce1 functions as a fatty acid transporter in Mtb and determine that facilitating cholesterol and fatty acid import via Rv3723/LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key function for Rv3723/LucA in in coordinating thetransport of both these substrates. DOI: http://dx.doi.org/10.7554/eLife.26969.001 eLife Sciences Publications, Ltd 2017-06-27 /pmc/articles/PMC5487216/ /pubmed/28708968 http://dx.doi.org/10.7554/eLife.26969 Text en © 2017, Nazarova et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Nazarova, Evgeniya V
Montague, Christine R
La, Thuy
Wilburn, Kaley M
Sukumar, Neelima
Lee, Wonsik
Caldwell, Shannon
Russell, David G
VanderVen, Brian C
Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis
title Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis
title_full Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis
title_fullStr Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis
title_full_unstemmed Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis
title_short Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis
title_sort rv3723/luca coordinates fatty acid and cholesterol uptake in mycobacterium tuberculosis
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487216/
https://www.ncbi.nlm.nih.gov/pubmed/28708968
http://dx.doi.org/10.7554/eLife.26969
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