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CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches
Copper is required for aerobic respiration by Mycobacterium tuberculosis and its human host, but this essential element is toxic in abundance. Copper nutritional immunity refers to host processes that modulate levels of free copper to alternately starve and intoxicate invading microbes. Bacteria eng...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147137/ https://www.ncbi.nlm.nih.gov/pubmed/35628523 http://dx.doi.org/10.3390/ijms23105713 |
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author | Shey-Njila, Oliver Hikal, Ahmed F. Gupta, Tuhina Sakamoto, Kaori Yahyaoui Azami, Hind Watford, Wendy T. Quinn, Frederick D. Karls, Russell K. |
author_facet | Shey-Njila, Oliver Hikal, Ahmed F. Gupta, Tuhina Sakamoto, Kaori Yahyaoui Azami, Hind Watford, Wendy T. Quinn, Frederick D. Karls, Russell K. |
author_sort | Shey-Njila, Oliver |
collection | PubMed |
description | Copper is required for aerobic respiration by Mycobacterium tuberculosis and its human host, but this essential element is toxic in abundance. Copper nutritional immunity refers to host processes that modulate levels of free copper to alternately starve and intoxicate invading microbes. Bacteria engulfed by macrophages are initially contained within copper-limited phagosomes, which fuse with ATP7A vesicles that pump in toxic levels of copper. In this report, we examine how CtpB, a P-type ATPase in M. tuberculosis, aids in response to nutritional immunity. In vitro, the induced expression of ctpB in copper-replete medium inhibited mycobacterial growth, while deletion of the gene impaired growth only in copper-starved medium and within copper-limited host cells, suggesting a role for CtpB in copper acquisition or export to the copper-dependent respiration supercomplex. Unexpectedly, the absence of ctpB resulted in hypervirulence in the DBA/2 mouse infection model. As ctpB null strains exhibit diminished growth only in copper-starved conditions, reduced copper transport may have enabled the mutant to acquire a “Goldilocks” amount of the metal during transit through copper-intoxicating environments within this model system. This work reveals CtpB as a component of the M. tuberculosis toolkit to counter host nutritional immunity and underscores the importance of elucidating copper-uptake mechanisms in pathogenic mycobacteria. |
format | Online Article Text |
id | pubmed-9147137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91471372022-05-29 CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches Shey-Njila, Oliver Hikal, Ahmed F. Gupta, Tuhina Sakamoto, Kaori Yahyaoui Azami, Hind Watford, Wendy T. Quinn, Frederick D. Karls, Russell K. Int J Mol Sci Article Copper is required for aerobic respiration by Mycobacterium tuberculosis and its human host, but this essential element is toxic in abundance. Copper nutritional immunity refers to host processes that modulate levels of free copper to alternately starve and intoxicate invading microbes. Bacteria engulfed by macrophages are initially contained within copper-limited phagosomes, which fuse with ATP7A vesicles that pump in toxic levels of copper. In this report, we examine how CtpB, a P-type ATPase in M. tuberculosis, aids in response to nutritional immunity. In vitro, the induced expression of ctpB in copper-replete medium inhibited mycobacterial growth, while deletion of the gene impaired growth only in copper-starved medium and within copper-limited host cells, suggesting a role for CtpB in copper acquisition or export to the copper-dependent respiration supercomplex. Unexpectedly, the absence of ctpB resulted in hypervirulence in the DBA/2 mouse infection model. As ctpB null strains exhibit diminished growth only in copper-starved conditions, reduced copper transport may have enabled the mutant to acquire a “Goldilocks” amount of the metal during transit through copper-intoxicating environments within this model system. This work reveals CtpB as a component of the M. tuberculosis toolkit to counter host nutritional immunity and underscores the importance of elucidating copper-uptake mechanisms in pathogenic mycobacteria. MDPI 2022-05-20 /pmc/articles/PMC9147137/ /pubmed/35628523 http://dx.doi.org/10.3390/ijms23105713 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shey-Njila, Oliver Hikal, Ahmed F. Gupta, Tuhina Sakamoto, Kaori Yahyaoui Azami, Hind Watford, Wendy T. Quinn, Frederick D. Karls, Russell K. CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches |
title | CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches |
title_full | CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches |
title_fullStr | CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches |
title_full_unstemmed | CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches |
title_short | CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches |
title_sort | ctpb facilitates mycobacterium tuberculosis growth in copper-limited niches |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147137/ https://www.ncbi.nlm.nih.gov/pubmed/35628523 http://dx.doi.org/10.3390/ijms23105713 |
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