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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24940

id CONICETDig_30f668e80bdbcf2be378737a86e3c277
oai_identifier_str oai:ri.conicet.gov.ar:11336/24940
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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)
instname_str 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
_version_ 1844614477243219968
score 13.070432