Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Shey-Njila, Oliver, Hikal, Ahmed F., Gupta, Tuhina, Sakamoto, Kaori, Yahyaoui Azami, Hind, Watford, Wendy T., Quinn, Frederick D., Karls, Russell K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784716734141300736
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
work_keys_str_mv AT sheynjilaoliver ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT hikalahmedf ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT guptatuhina ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT sakamotokaori ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT yahyaouiazamihind ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT watfordwendyt ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT quinnfrederickd ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches
AT karlsrussellk ctpbfacilitatesmycobacteriumtuberculosisgrowthincopperlimitedniches