Brucella abortus depends on L-serine biosynthesis for intracellular proliferation

Autores
Revora, Virginia; Marchesini, Maria Ines; Comerci, Diego José
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
L-Serine is a nonessential amino acid and a key intermediate in several relevant metabolic pathways. In bacteria, the major source of L-serine is the phosphorylated pathway, which comprises three enzymes: D-3-phosphoglycerate dehydrogenase (PGDH; SerA), phosphoserine amino transferase (PSAT; SerC), and L-phosphoserine phosphatase (PSP; SerB). The Brucella abortus genome encodes two PGDHs (SerA-1 and SerA-2), involved in the first step in L-serine biosynthesis, and one PSAT and one PSP, responsible for the second and third steps, respectively. In this study, we demonstrate that the serA1 serA2 double mutant and the serC and serB single mutants are auxotrophic for L-serine. These auxotrophic mutants can be internalized but are unable to replicate in HeLa cells and in J774A.1 macrophage-like cells. Replication defects of auxotrophic mutants can be reverted by cell medium supplementation with L-serine at early times postinfection. In addition, the serB mutant is attenuated in the murine intraperitoneal infection model and has an altered lipid composition, since the lack of L-serine abrogates phosphatidylethanolamine synthesis in this strain. Taken together, these results reveal that limited availability of L-serine within the host cell impairs proliferation of the auxotrophic strains, highlighting the relevance of this biosynthetic pathway in Brucella pathogenicity.
Fil: Revora, Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Marchesini, Maria Ines. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Comerci, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina
Materia
BIOSYNTHESIS
BRUCELLA
L-SERINE
VIRULENCE
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:11336/151406
Acceder
id CONICETDig_c310c2efed16623d6f7c7697cf5f528d
oai_identifier_str oai:ri.conicet.gov.ar:11336/151406
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Brucella abortus depends on L-serine biosynthesis for intracellular proliferationRevora, VirginiaMarchesini, Maria InesComerci, Diego JoséBIOSYNTHESISBRUCELLAL-SERINEVIRULENCEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1L-Serine is a nonessential amino acid and a key intermediate in several relevant metabolic pathways. In bacteria, the major source of L-serine is the phosphorylated pathway, which comprises three enzymes: D-3-phosphoglycerate dehydrogenase (PGDH; SerA), phosphoserine amino transferase (PSAT; SerC), and L-phosphoserine phosphatase (PSP; SerB). The Brucella abortus genome encodes two PGDHs (SerA-1 and SerA-2), involved in the first step in L-serine biosynthesis, and one PSAT and one PSP, responsible for the second and third steps, respectively. In this study, we demonstrate that the serA1 serA2 double mutant and the serC and serB single mutants are auxotrophic for L-serine. These auxotrophic mutants can be internalized but are unable to replicate in HeLa cells and in J774A.1 macrophage-like cells. Replication defects of auxotrophic mutants can be reverted by cell medium supplementation with L-serine at early times postinfection. In addition, the serB mutant is attenuated in the murine intraperitoneal infection model and has an altered lipid composition, since the lack of L-serine abrogates phosphatidylethanolamine synthesis in this strain. Taken together, these results reveal that limited availability of L-serine within the host cell impairs proliferation of the auxotrophic strains, highlighting the relevance of this biosynthetic pathway in Brucella pathogenicity.Fil: Revora, Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Marchesini, Maria Ines. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Comerci, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; ArgentinaAmerican Society for Microbiology2019-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/151406Revora, Virginia; Marchesini, Maria Ines; Comerci, Diego José; Brucella abortus depends on L-serine biosynthesis for intracellular proliferation; American Society for Microbiology; Infection and Immunity; 88; 2; 11-2019; 1-400019-9567CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/lookup/doi/10.1128/IAI.00840-19info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00840-19info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:54:28Zoai:ri.conicet.gov.ar:11336/151406instacron: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 09:54:28.69CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
title Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
spellingShingle Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
Revora, Virginia
BIOSYNTHESIS
BRUCELLA
L-SERINE
VIRULENCE
title_short Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
title_full Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
title_fullStr Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
title_full_unstemmed Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
title_sort Brucella abortus depends on L-serine biosynthesis for intracellular proliferation
dc.creator.none.fl_str_mv Revora, Virginia
Marchesini, Maria Ines
Comerci, Diego José
author Revora, Virginia
author_facet Revora, Virginia
Marchesini, Maria Ines
Comerci, Diego José
author_role author
author2 Marchesini, Maria Ines
Comerci, Diego José
author2_role author
author
dc.subject.none.fl_str_mv BIOSYNTHESIS
BRUCELLA
L-SERINE
VIRULENCE
topic BIOSYNTHESIS
BRUCELLA
L-SERINE
VIRULENCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv L-Serine is a nonessential amino acid and a key intermediate in several relevant metabolic pathways. In bacteria, the major source of L-serine is the phosphorylated pathway, which comprises three enzymes: D-3-phosphoglycerate dehydrogenase (PGDH; SerA), phosphoserine amino transferase (PSAT; SerC), and L-phosphoserine phosphatase (PSP; SerB). The Brucella abortus genome encodes two PGDHs (SerA-1 and SerA-2), involved in the first step in L-serine biosynthesis, and one PSAT and one PSP, responsible for the second and third steps, respectively. In this study, we demonstrate that the serA1 serA2 double mutant and the serC and serB single mutants are auxotrophic for L-serine. These auxotrophic mutants can be internalized but are unable to replicate in HeLa cells and in J774A.1 macrophage-like cells. Replication defects of auxotrophic mutants can be reverted by cell medium supplementation with L-serine at early times postinfection. In addition, the serB mutant is attenuated in the murine intraperitoneal infection model and has an altered lipid composition, since the lack of L-serine abrogates phosphatidylethanolamine synthesis in this strain. Taken together, these results reveal that limited availability of L-serine within the host cell impairs proliferation of the auxotrophic strains, highlighting the relevance of this biosynthetic pathway in Brucella pathogenicity.
Fil: Revora, Virginia. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Marchesini, Maria Ines. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Comerci, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina
description L-Serine is a nonessential amino acid and a key intermediate in several relevant metabolic pathways. In bacteria, the major source of L-serine is the phosphorylated pathway, which comprises three enzymes: D-3-phosphoglycerate dehydrogenase (PGDH; SerA), phosphoserine amino transferase (PSAT; SerC), and L-phosphoserine phosphatase (PSP; SerB). The Brucella abortus genome encodes two PGDHs (SerA-1 and SerA-2), involved in the first step in L-serine biosynthesis, and one PSAT and one PSP, responsible for the second and third steps, respectively. In this study, we demonstrate that the serA1 serA2 double mutant and the serC and serB single mutants are auxotrophic for L-serine. These auxotrophic mutants can be internalized but are unable to replicate in HeLa cells and in J774A.1 macrophage-like cells. Replication defects of auxotrophic mutants can be reverted by cell medium supplementation with L-serine at early times postinfection. In addition, the serB mutant is attenuated in the murine intraperitoneal infection model and has an altered lipid composition, since the lack of L-serine abrogates phosphatidylethanolamine synthesis in this strain. Taken together, these results reveal that limited availability of L-serine within the host cell impairs proliferation of the auxotrophic strains, highlighting the relevance of this biosynthetic pathway in Brucella pathogenicity.
publishDate 2019
dc.date.none.fl_str_mv 2019-11
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/11336/151406
Revora, Virginia; Marchesini, Maria Ines; Comerci, Diego José; Brucella abortus depends on L-serine biosynthesis for intracellular proliferation; American Society for Microbiology; Infection and Immunity; 88; 2; 11-2019; 1-40
0019-9567
CONICET Digital
CONICET
url http://hdl.handle.net/11336/151406
identifier_str_mv Revora, Virginia; Marchesini, Maria Ines; Comerci, Diego José; Brucella abortus depends on L-serine biosynthesis for intracellular proliferation; American Society for Microbiology; Infection and Immunity; 88; 2; 11-2019; 1-40
0019-9567
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://iai.asm.org/lookup/doi/10.1128/IAI.00840-19
info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00840-19
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
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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_ 1844613654216966144
score 13.070432

Publicaciones similares