Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms
Yves-Marie Boudehen
(1, 2)
,
Marion Faucher
(1)
,
Xavier Maréchal
(3, 4)
,
Roger Miras
(3)
,
Jérôme Rech
(5)
,
Yoann Rombouts
(1)
,
Olivier Sénèque
(6)
,
Maximilian Wallat
(1, 7)
,
Pascal Demange
(1)
,
Jean-Yves Bouet
(5)
,
Olivier Saurel
(1)
,
Patrice Catty
(3)
,
Claude Gutierrez
(1)
,
Olivier Neyrolles
(1)
1
Tuberculose et biologie des infections [IPBS, Toulouse]
2 IRIM - Institut de Recherche en Infectiologie de Montpellier
3 BEE - BioEnergie et Environnement
4 Evotec [Toulouse]
5 LMGM - Laboratoire de microbiologie et génétique moléculaires - UMR5100
6 PMB - Physiochimie des Métaux
7 LSHTM - London School of Hygiene and Tropical Medicine
2 IRIM - Institut de Recherche en Infectiologie de Montpellier
3 BEE - BioEnergie et Environnement
4 Evotec [Toulouse]
5 LMGM - Laboratoire de microbiologie et génétique moléculaires - UMR5100
6 PMB - Physiochimie des Métaux
7 LSHTM - London School of Hygiene and Tropical Medicine
Yves-Marie Boudehen
- Fonction : Auteur
- PersonId : 1389195
- ORCID : 0000-0003-0021-276X
- IdRef : 254346162
Yoann Rombouts
- Fonction : Auteur
- PersonId : 739107
- IdHAL : yoann-rombouts
- ORCID : 0000-0003-4482-2199
- IdRef : 153100370
Pascal Demange
- Fonction : Auteur
- PersonId : 741316
- IdHAL : pascal-demange
- ORCID : 0000-0002-9572-9990
- IdRef : 033686025
Olivier Saurel
- Fonction : Auteur
- PersonId : 1005751
- IdRef : 178046205
Claude Gutierrez
- Fonction : Auteur
- PersonId : 1079629
- ORCID : 0000-0003-1777-0223
- IdRef : 061722146
Olivier Neyrolles
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 178826
- IdHAL : olivier-neyrolles
- ORCID : 0000-0003-0047-5885
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Connectez-vous pour contacter l'auteur
Résumé
The human pathogen Mycobacterium tuberculosis requires a P-1B-ATPase metal exporter, CtpC (Rv3270), for resistance to zinc poisoning. Here, we show that zinc resistance also depends on a chaperone-like protein, PacL1 (Rv3269). PacL1 contains a transmembrane domain, a cytoplasmic region with glutamine/alanine repeats and a C-terminal metal-binding motif (MBM). PacL1 binds Zn2+, but the MBM is required only at high zinc concentrations. PacL1 co-localizes with CtpC in dynamic foci in the mycobacterial plasma membrane, and the two proteins form high molecular weight complexes. Foci formation does not require flotillin nor the PacL1 MBM. However, deletion of the PacL1 Glu/Ala repeats leads to loss of CtpC and sensitivity to zinc. Genes pacL1 and ctpC appear to be in the same operon, and homologous gene pairs are found in the genomes of other bacteria. Furthermore, PacL1 colocalizes and functions redundantly with other PacL orthologs in M. tuberculosis. Overall, our results indicate that PacL proteins may act as scaffolds that assemble P-ATPase-containing metal efflux platforms mediating bacterial resistance to metal poisoning.
The human pathogen Mycobacterium tuberculosis requires a metal exporter, CtpC, for resistance to zinc poisoning. Here, the authors show that zinc resistance also depends on a chaperone-like protein that binds zinc ions, forms high-molecular-weight complexes with CtpC in the cytoplasmic membrane, and is required for CtpC function.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Résumé |
en
The human pathogen Mycobacterium tuberculosis requires a P-1B-ATPase metal exporter, CtpC (Rv3270), for resistance to zinc poisoning. Here, we show that zinc resistance also depends on a chaperone-like protein, PacL1 (Rv3269). PacL1 contains a transmembrane domain, a cytoplasmic region with glutamine/alanine repeats and a C-terminal metal-binding motif (MBM). PacL1 binds Zn2+, but the MBM is required only at high zinc concentrations. PacL1 co-localizes with CtpC in dynamic foci in the mycobacterial plasma membrane, and the two proteins form high molecular weight complexes. Foci formation does not require flotillin nor the PacL1 MBM. However, deletion of the PacL1 Glu/Ala repeats leads to loss of CtpC and sensitivity to zinc. Genes pacL1 and ctpC appear to be in the same operon, and homologous gene pairs are found in the genomes of other bacteria. Furthermore, PacL1 colocalizes and functions redundantly with other PacL orthologs in M. tuberculosis. Overall, our results indicate that PacL proteins may act as scaffolds that assemble P-ATPase-containing metal efflux platforms mediating bacterial resistance to metal poisoning.
The human pathogen Mycobacterium tuberculosis requires a metal exporter, CtpC, for resistance to zinc poisoning. Here, the authors show that zinc resistance also depends on a chaperone-like protein that binds zinc ions, forms high-molecular-weight complexes with CtpC in the cytoplasmic membrane, and is required for CtpC function.
|
Titre |
en
Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms
|
Auteur(s) |
Yves-Marie Boudehen
1, 2
, Marion Faucher
1
, Xavier Maréchal
3, 4
, Roger Miras
3
, Jérôme Rech
5
, Yoann Rombouts
1
, Olivier Sénèque
6
, Maximilian Wallat
1, 7
, Pascal Demange
1
, Jean-Yves Bouet
5
, Olivier Saurel
1
, Patrice Catty
3
, Claude Gutierrez
1
, Olivier Neyrolles
1
1
Tuberculose et biologie des infections [IPBS, Toulouse]
( 1039589 )
- Université Toulouse III-Paul Sabatier
BP 64182
205 route de Narbonne
31077 Toulouse Cedex 04
- France
2
IRIM -
Institut de Recherche en Infectiologie de Montpellier
( 1100763 )
- UMR 9004, 1919 Route de Mende - 34293 Montpellier
- France
3
BEE -
BioEnergie et Environnement
( 1061077 )
- 17 rue des Martyrs 38054 Grenoble cedex
- France
4
Evotec [Toulouse]
( 1072313 )
- Campus Curie,
195, route d‘Espagne,
31036 Toulouse,
France
- France
5
LMGM -
Laboratoire de microbiologie et génétique moléculaires - UMR5100
( 592 )
- 118 route de Narbonne 31062 Toulouse cedex 9
- France
6
PMB -
Physiochimie des Métaux
( 1043292 )
- 17, avenue des Martyrs 38 054 Grenoble cedex 09
- France
7
LSHTM -
London School of Hygiene and Tropical Medicine
( 353798 )
- Keppel Street
London
WC1E 7HT
- Royaume-Uni
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2022-08-12
|
Volume |
13
|
Numéro |
1
|
Page/Identifiant |
4731
|
Licence |
Paternité
|
Langue du document |
Anglais
|
Domaine(s) |
|
Mots-clés (Mesh) |
|
Projet(s) ANR |
|
Mots-clés |
en
Bacterial pathogenesis, Pathogens
|
DOI | 10.1038/s41467-022-32085-7 |
Pubmed Id | 35961955 |
PubMed Central | PMC9374683 |
Origine :
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