Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms
Yves-Marie Boudehen
- Fonction : Auteur
- PersonId : 1389195
- ORCID : 0000-0003-0021-276X
- IdRef : 254346162
Marion Faucher
- Fonction : Auteur
- PersonId : 759110
- ORCID : 0000-0003-4306-3178
Xavier Maréchal
- Fonction : Auteur
- PersonId : 768873
- ORCID : 0000-0001-6399-7811
Roger Miras
- Fonction : Auteur
Jérôme Rech
- Fonction : Auteur
Olivier Sénèque
- Fonction : Auteur
Maximilian Wallat
- Fonction : Auteur
Pascal Demange
- Fonction : Auteur
- PersonId : 741316
- IdHAL : pascal-demange
- ORCID : 0000-0002-9572-9990
- IdRef : 033686025
Jean-Yves Bouet
- Fonction : Auteur
- PersonId : 181812
- IdHAL : jean-yves-bouet
- ORCID : 0000-0003-1488-5455
- IdRef : 142527009
Olivier Saurel
- Fonction : Auteur
- PersonId : 1005751
- IdRef : 178046205
Patrice Catty
- Fonction : Auteur
- PersonId : 761093
- ORCID : 0000-0001-8727-9304
Claude Gutierrez
- Fonction : Auteur
- PersonId : 1079629
- ORCID : 0000-0003-1777-0223
- IdRef : 061722146
Olivier Neyrolles
- Fonction : Auteur
- PersonId : 178826
- IdHAL : olivier-neyrolles
- ORCID : 0000-0003-0047-5885
- IdRef : 057428050
Résumé
Transition metals are toxic at high concentrations. The P 1B -ATPase metal exporter CtpC/Rv3270 is required for resistance to zinc poisoning in the human pathogen Mycobacterium tuberculosis . Here, we discovered that zinc resistance also depends on the chaperone-like protein PacL1/Rv3269. PacL1 bound Zn 2+ , but unlike PacL1 and CtpC, the PacL1 metal-binding motif (MBM) was required only at high zinc concentrations. PacL1 co-localized with CtpC in dynamic microdomains within the mycobacterial plasma membrane. Microdomain formation did not require flotillins nor the PacL1 MBM. Instead, loss of the PacL1 Glutamine/Alanine repeats led to loss of CtpC and sensitivity to zinc. PacL1 and CtpC are within the same operon, and homologous PacL1-P 1B -ATPase pairs are widely distributed within and across prokaryotes. PacL1 colocalized and functioned redundantly with PacL orthologs in Mycobacterium tuberculosis . Overall, our study suggests that PacL proteins are scaffolds that assemble P-ATPase-containing metal efflux platforms, a novel type of functional membrane microdomain that underlies bacterial resistance to metal poisoning.
Domaines
Sciences du Vivant [q-bio]Format du dépôt | Notice |
---|---|
Type de dépôt | Pré-publication, Document de travail |
Résumé |
en
Transition metals are toxic at high concentrations. The P 1B -ATPase metal exporter CtpC/Rv3270 is required for resistance to zinc poisoning in the human pathogen Mycobacterium tuberculosis . Here, we discovered that zinc resistance also depends on the chaperone-like protein PacL1/Rv3269. PacL1 bound Zn 2+ , but unlike PacL1 and CtpC, the PacL1 metal-binding motif (MBM) was required only at high zinc concentrations. PacL1 co-localized with CtpC in dynamic microdomains within the mycobacterial plasma membrane. Microdomain formation did not require flotillins nor the PacL1 MBM. Instead, loss of the PacL1 Glutamine/Alanine repeats led to loss of CtpC and sensitivity to zinc. PacL1 and CtpC are within the same operon, and homologous PacL1-P 1B -ATPase pairs are widely distributed within and across prokaryotes. PacL1 colocalized and functioned redundantly with PacL orthologs in Mycobacterium tuberculosis . Overall, our study suggests that PacL proteins are scaffolds that assemble P-ATPase-containing metal efflux platforms, a novel type of functional membrane microdomain that underlies bacterial resistance to metal poisoning.
|
Titre |
en
Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms
|
Auteur(s) |
Yves-Marie Boudehen
, Marion Faucher
, Xavier Maréchal
, Roger Miras
, Jérôme Rech
, Olivier Sénèque
, Maximilian Wallat
, Pascal Demange
, Jean-Yves Bouet
, Olivier Saurel
, Patrice Catty
, Claude Gutierrez
, Olivier Neyrolles
1
1
IPBS -
Institut de pharmacologie et de biologie structurale
( 583 )
- 205 Route de Narbonne 31077 TOULOUSE CEDEX 4
- France
|
Langue du document |
Anglais
|
Domaine(s) |
|
BioRxiv | 2021.10.01.462712 |
DOI | 10.1101/2021.10.01.462712 |
Loading...