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A vitamin B(12) transporter in Mycobacterium tuberculosis

Vitamin B(12)-dependent enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B(12) in vitro, it is uncertain whether the organism is able to scavenge B(12) during h...

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Autores principales: Gopinath, Krishnamoorthy, Venclovas, Česlovas, Ioerger, Thomas R., Sacchettini, James C., McKinney, John D., Mizrahi, Valerie, Warner, Digby F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603451/
https://www.ncbi.nlm.nih.gov/pubmed/23407640
http://dx.doi.org/10.1098/rsob.120175
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author Gopinath, Krishnamoorthy
Venclovas, Česlovas
Ioerger, Thomas R.
Sacchettini, James C.
McKinney, John D.
Mizrahi, Valerie
Warner, Digby F.
author_facet Gopinath, Krishnamoorthy
Venclovas, Česlovas
Ioerger, Thomas R.
Sacchettini, James C.
McKinney, John D.
Mizrahi, Valerie
Warner, Digby F.
author_sort Gopinath, Krishnamoorthy
collection PubMed
description Vitamin B(12)-dependent enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B(12) in vitro, it is uncertain whether the organism is able to scavenge B(12) during host infection. This question is crucial to predictions of metabolic function, but its resolution is complicated by the absence in the M. tuberculosis genome of a direct homologue of BtuFCD, the only bacterial B(12) transport system described to date. We applied genome-wide transposon mutagenesis to identify M. tuberculosis mutants defective in their ability to use exogenous B(12). A small proportion of these mapped to Rv1314c, identifying the putative PduO-type ATP : co(I)rrinoid adenosyltransferase as essential for B(12) assimilation. Most notably, however, insertions in Rv1819c dominated the mutant pool, revealing an unexpected function in B(12) acquisition for an ATP-binding cassette (ABC)-type protein previously investigated as the mycobacterial BacA homologue. Moreover, targeted deletion of Rv1819c eliminated the ability of M. tuberculosis to transport B(12) and related corrinoids in vitro. Our results establish an alternative to the canonical BtuCD-type system for B(12) uptake in M. tuberculosis, and elucidate a role in B(12) metabolism for an ABC protein implicated in chronic mycobacterial infection.
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spelling pubmed-36034512013-03-27 A vitamin B(12) transporter in Mycobacterium tuberculosis Gopinath, Krishnamoorthy Venclovas, Česlovas Ioerger, Thomas R. Sacchettini, James C. McKinney, John D. Mizrahi, Valerie Warner, Digby F. Open Biol Research Vitamin B(12)-dependent enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B(12) in vitro, it is uncertain whether the organism is able to scavenge B(12) during host infection. This question is crucial to predictions of metabolic function, but its resolution is complicated by the absence in the M. tuberculosis genome of a direct homologue of BtuFCD, the only bacterial B(12) transport system described to date. We applied genome-wide transposon mutagenesis to identify M. tuberculosis mutants defective in their ability to use exogenous B(12). A small proportion of these mapped to Rv1314c, identifying the putative PduO-type ATP : co(I)rrinoid adenosyltransferase as essential for B(12) assimilation. Most notably, however, insertions in Rv1819c dominated the mutant pool, revealing an unexpected function in B(12) acquisition for an ATP-binding cassette (ABC)-type protein previously investigated as the mycobacterial BacA homologue. Moreover, targeted deletion of Rv1819c eliminated the ability of M. tuberculosis to transport B(12) and related corrinoids in vitro. Our results establish an alternative to the canonical BtuCD-type system for B(12) uptake in M. tuberculosis, and elucidate a role in B(12) metabolism for an ABC protein implicated in chronic mycobacterial infection. The Royal Society 2013-02 /pmc/articles/PMC3603451/ /pubmed/23407640 http://dx.doi.org/10.1098/rsob.120175 Text en http://creativecommons.org/licenses/by/3.0/ © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Gopinath, Krishnamoorthy
Venclovas, Česlovas
Ioerger, Thomas R.
Sacchettini, James C.
McKinney, John D.
Mizrahi, Valerie
Warner, Digby F.
A vitamin B(12) transporter in Mycobacterium tuberculosis
title A vitamin B(12) transporter in Mycobacterium tuberculosis
title_full A vitamin B(12) transporter in Mycobacterium tuberculosis
title_fullStr A vitamin B(12) transporter in Mycobacterium tuberculosis
title_full_unstemmed A vitamin B(12) transporter in Mycobacterium tuberculosis
title_short A vitamin B(12) transporter in Mycobacterium tuberculosis
title_sort vitamin b(12) transporter in mycobacterium tuberculosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603451/
https://www.ncbi.nlm.nih.gov/pubmed/23407640
http://dx.doi.org/10.1098/rsob.120175
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