A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria
- Autores
- Padilla Benavides, Teresita; Long, Jarukit E.; Raimunda, Daniel Cesar; Sassetti, Christopher M.; Argüello, José M.
- Año de publicación
- 2013
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux, and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-ATPase, CtpC, is required for Mycobacterium tuberculosis survival in a mouse model (Sassetti and Rubin (2003) Proc. Nat. Acad. Sci. 100, 12989-12994). CtpC prevents Zn2+ toxicity, suggesting a role in Zn2+ export from the cytosol (Botella, et al., (2011) Cell Host Microbe 10, 248-259). However, key metal coordinating residues and overall structure of CtpC are distinct from Zn2+-ATPases. We found that isolated CtpC has metal dependent ATPase activity with a strong preference for Mn2+ over Zn2+ . In vivo, CtpC is unable to complement Escherichia coli lacking a functional Zn2+-ATPase. Deletion of M. tuberculosis or M. smegmatis ctpC leads to cytosolic Mn2+ accumulation but no alterations in other metals levels. While ctpC-deficient M. tuberculosis is sensitive to extracellular Zn2+ , the M. smegmatis mutant is not. Both ctpC mutants are sensitive to oxidative stress, which might explain the Zn2+-sensitive phenotype of the M. tuberculosis ctpC mutant. CtpC is a high affinity/slow turnover ATPase, suggesting a role in protein metallation. Consistent with this hypothesis, mutation of CtpC leads to a decrease of Mn2+-bound to secreted proteins and of the activity of secreted Fe/Mnsuperoxide dismutase, particularly in M. smegmatis. Alterations in the assembly of metalloenzymes involved in redox stress response might explain the sensitivity of M. tuberculosis ctpC mutants to oxidative stress, grow and persistence defects in mice infection models.
Fil: Padilla Benavides, Teresita. Worcester Polytechnic Institute; Estados Unidos
Fil: Long, Jarukit E.. University Of Massachussets. Medical School; Estados Unidos
Fil: Raimunda, Daniel Cesar. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sassetti, Christopher M.. University Of Massachussets. Medical School; Estados Unidos. Howard Hughes Medical Institute; Estados Unidos
Fil: Argüello, José M.. Worcester Polytechnic Institute; Estados Unidos - Materia
-
CtpC
Mn2+-ATPase
SodA
Mycobacterium tuberculosis - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/24940
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A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteriaPadilla Benavides, TeresitaLong, Jarukit E.Raimunda, Daniel CesarSassetti, Christopher M.Argüello, José M.CtpCMn2+-ATPaseSodAMycobacterium tuberculosishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux, and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-ATPase, CtpC, is required for Mycobacterium tuberculosis survival in a mouse model (Sassetti and Rubin (2003) Proc. Nat. Acad. Sci. 100, 12989-12994). CtpC prevents Zn2+ toxicity, suggesting a role in Zn2+ export from the cytosol (Botella, et al., (2011) Cell Host Microbe 10, 248-259). However, key metal coordinating residues and overall structure of CtpC are distinct from Zn2+-ATPases. We found that isolated CtpC has metal dependent ATPase activity with a strong preference for Mn2+ over Zn2+ . In vivo, CtpC is unable to complement Escherichia coli lacking a functional Zn2+-ATPase. Deletion of M. tuberculosis or M. smegmatis ctpC leads to cytosolic Mn2+ accumulation but no alterations in other metals levels. While ctpC-deficient M. tuberculosis is sensitive to extracellular Zn2+ , the M. smegmatis mutant is not. Both ctpC mutants are sensitive to oxidative stress, which might explain the Zn2+-sensitive phenotype of the M. tuberculosis ctpC mutant. CtpC is a high affinity/slow turnover ATPase, suggesting a role in protein metallation. Consistent with this hypothesis, mutation of CtpC leads to a decrease of Mn2+-bound to secreted proteins and of the activity of secreted Fe/Mnsuperoxide dismutase, particularly in M. smegmatis. Alterations in the assembly of metalloenzymes involved in redox stress response might explain the sensitivity of M. tuberculosis ctpC mutants to oxidative stress, grow and persistence defects in mice infection models.Fil: Padilla Benavides, Teresita. Worcester Polytechnic Institute; Estados UnidosFil: Long, Jarukit E.. University Of Massachussets. Medical School; Estados UnidosFil: Raimunda, Daniel Cesar. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sassetti, Christopher M.. University Of Massachussets. Medical School; Estados Unidos. Howard Hughes Medical Institute; Estados UnidosFil: Argüello, José M.. Worcester Polytechnic Institute; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24940Padilla Benavides, Teresita; Long, Jarukit E.; Raimunda, Daniel Cesar; Sassetti, Christopher M.; Argüello, José M.; A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 288; 3-2013; 11334-113470021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/288/16/11334info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M112.448175info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630897/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:44:03Zoai:ri.conicet.gov.ar:11336/24940instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:44:03.297CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
title |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
spellingShingle |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria Padilla Benavides, Teresita CtpC Mn2+-ATPase SodA Mycobacterium tuberculosis |
title_short |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
title_full |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
title_fullStr |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
title_full_unstemmed |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
title_sort |
A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria |
dc.creator.none.fl_str_mv |
Padilla Benavides, Teresita Long, Jarukit E. Raimunda, Daniel Cesar Sassetti, Christopher M. Argüello, José M. |
author |
Padilla Benavides, Teresita |
author_facet |
Padilla Benavides, Teresita Long, Jarukit E. Raimunda, Daniel Cesar Sassetti, Christopher M. Argüello, José M. |
author_role |
author |
author2 |
Long, Jarukit E. Raimunda, Daniel Cesar Sassetti, Christopher M. Argüello, José M. |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
CtpC Mn2+-ATPase SodA Mycobacterium tuberculosis |
topic |
CtpC Mn2+-ATPase SodA Mycobacterium tuberculosis |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux, and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-ATPase, CtpC, is required for Mycobacterium tuberculosis survival in a mouse model (Sassetti and Rubin (2003) Proc. Nat. Acad. Sci. 100, 12989-12994). CtpC prevents Zn2+ toxicity, suggesting a role in Zn2+ export from the cytosol (Botella, et al., (2011) Cell Host Microbe 10, 248-259). However, key metal coordinating residues and overall structure of CtpC are distinct from Zn2+-ATPases. We found that isolated CtpC has metal dependent ATPase activity with a strong preference for Mn2+ over Zn2+ . In vivo, CtpC is unable to complement Escherichia coli lacking a functional Zn2+-ATPase. Deletion of M. tuberculosis or M. smegmatis ctpC leads to cytosolic Mn2+ accumulation but no alterations in other metals levels. While ctpC-deficient M. tuberculosis is sensitive to extracellular Zn2+ , the M. smegmatis mutant is not. Both ctpC mutants are sensitive to oxidative stress, which might explain the Zn2+-sensitive phenotype of the M. tuberculosis ctpC mutant. CtpC is a high affinity/slow turnover ATPase, suggesting a role in protein metallation. Consistent with this hypothesis, mutation of CtpC leads to a decrease of Mn2+-bound to secreted proteins and of the activity of secreted Fe/Mnsuperoxide dismutase, particularly in M. smegmatis. Alterations in the assembly of metalloenzymes involved in redox stress response might explain the sensitivity of M. tuberculosis ctpC mutants to oxidative stress, grow and persistence defects in mice infection models. Fil: Padilla Benavides, Teresita. Worcester Polytechnic Institute; Estados Unidos Fil: Long, Jarukit E.. University Of Massachussets. Medical School; Estados Unidos Fil: Raimunda, Daniel Cesar. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sassetti, Christopher M.. University Of Massachussets. Medical School; Estados Unidos. Howard Hughes Medical Institute; Estados Unidos Fil: Argüello, José M.. Worcester Polytechnic Institute; Estados Unidos |
description |
Transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux, and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-ATPase, CtpC, is required for Mycobacterium tuberculosis survival in a mouse model (Sassetti and Rubin (2003) Proc. Nat. Acad. Sci. 100, 12989-12994). CtpC prevents Zn2+ toxicity, suggesting a role in Zn2+ export from the cytosol (Botella, et al., (2011) Cell Host Microbe 10, 248-259). However, key metal coordinating residues and overall structure of CtpC are distinct from Zn2+-ATPases. We found that isolated CtpC has metal dependent ATPase activity with a strong preference for Mn2+ over Zn2+ . In vivo, CtpC is unable to complement Escherichia coli lacking a functional Zn2+-ATPase. Deletion of M. tuberculosis or M. smegmatis ctpC leads to cytosolic Mn2+ accumulation but no alterations in other metals levels. While ctpC-deficient M. tuberculosis is sensitive to extracellular Zn2+ , the M. smegmatis mutant is not. Both ctpC mutants are sensitive to oxidative stress, which might explain the Zn2+-sensitive phenotype of the M. tuberculosis ctpC mutant. CtpC is a high affinity/slow turnover ATPase, suggesting a role in protein metallation. Consistent with this hypothesis, mutation of CtpC leads to a decrease of Mn2+-bound to secreted proteins and of the activity of secreted Fe/Mnsuperoxide dismutase, particularly in M. smegmatis. Alterations in the assembly of metalloenzymes involved in redox stress response might explain the sensitivity of M. tuberculosis ctpC mutants to oxidative stress, grow and persistence defects in mice infection models. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-03 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/24940 Padilla Benavides, Teresita; Long, Jarukit E.; Raimunda, Daniel Cesar; Sassetti, Christopher M.; Argüello, José M.; A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 288; 3-2013; 11334-11347 0021-9258 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/24940 |
identifier_str_mv |
Padilla Benavides, Teresita; Long, Jarukit E.; Raimunda, Daniel Cesar; Sassetti, Christopher M.; Argüello, José M.; A Novel P1B-type Mn2+-transporting ATPase is required for secreted protein Metallation in mycobacteria; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 288; 3-2013; 11334-11347 0021-9258 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/288/16/11334 info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M112.448175 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630897/ |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Society for Biochemistry and Molecular Biology |
publisher.none.fl_str_mv |
American Society for Biochemistry and Molecular Biology |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614477243219968 |
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13.070432 |