A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence

Horizontal gene transfer has shaped the evolution of Salmonella enterica as pathogen. Some functions acquired by this mechanism include enzymes involved in peptidoglycan (PG) synthesis and remodeling. Here, we report a novel serovar Typhimurium protein that is absent in non-pathogenic bacteria and b...

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Autores: Cestero, Juan J., Castanheira, Sónia, Pucciarelli, María Graciela, García del Portillo, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/262324
Acceso en línea:http://hdl.handle.net/10261/262324
Access Level:acceso abierto
Palabra clave:Salmonella
Peptidoglycan
Periplasm
MltD
Regulation
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spelling A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and VirulenceCestero, Juan J.Castanheira, SóniaPucciarelli, María GracielaGarcía del Portillo, FranciscoSalmonellaPeptidoglycanPeriplasmMltDRegulationHorizontal gene transfer has shaped the evolution of Salmonella enterica as pathogen. Some functions acquired by this mechanism include enzymes involved in peptidoglycan (PG) synthesis and remodeling. Here, we report a novel serovar Typhimurium protein that is absent in non-pathogenic bacteria and bears a LprI functional domain, first reported in a Mycobacterium tuberculosis lipoprotein conferring lysozyme resistance. Based on the presence of such domain, we hypothesized a role of this S. Typhimurium protein in PG metabolism. This protein, which we named ScwA for Salmonella cell wall-related regulator-A, controls positively the levels of the murein lytic transglycosylase MltD. In addition, the levels of other enzymes that cleave bonds in the PG lattice were affected in a mutant lacking ScwA, including a soluble lytic tranglycosylase (Slt), the amidase AmiC, and a few endo- and carboxypeptidases (NlpC, PBP4, and AmpH). The scwA gene has lower G+C content than the genomic average (43.1 vs. 52.2%), supporting acquisition by horizontal transfer. ScwA is located in the periplasm, stabilized by two disulfide bridges, produced preferentially in stationary phase and down-regulated following entry of the pathogen into eukaryotic cells. ScwA deficiency, however, results in a hypervirulent phenotype in the murine typhoid model. Based on these findings, we conclude that ScwA may be exploited by S. Typhimurium to ensure cell envelope homeostasis along the infection and to prevent host overt damage. This role could be accomplished by controlling the production or stability of a reduced number of peptidoglycan hydrolases whose activities result in the release of PG fragments.Ministry of Science and InnovationMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/262324reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3389/fmicb.2021.633701Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2623242026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
title A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
spellingShingle A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
Cestero, Juan J.
Salmonella
Peptidoglycan
Periplasm
MltD
Regulation
title_short A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
title_full A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
title_fullStr A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
title_full_unstemmed A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
title_sort A Novel Salmonella Periplasmic Protein Controlling Cell Wall Homeostasis and Virulence
dc.creator.none.fl_str_mv Cestero, Juan J.
Castanheira, Sónia
Pucciarelli, María Graciela
García del Portillo, Francisco
author Cestero, Juan J.
author_facet Cestero, Juan J.
Castanheira, Sónia
Pucciarelli, María Graciela
García del Portillo, Francisco
author_role author
author2 Castanheira, Sónia
Pucciarelli, María Graciela
García del Portillo, Francisco
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Salmonella
Peptidoglycan
Periplasm
MltD
Regulation
topic Salmonella
Peptidoglycan
Periplasm
MltD
Regulation
description Horizontal gene transfer has shaped the evolution of Salmonella enterica as pathogen. Some functions acquired by this mechanism include enzymes involved in peptidoglycan (PG) synthesis and remodeling. Here, we report a novel serovar Typhimurium protein that is absent in non-pathogenic bacteria and bears a LprI functional domain, first reported in a Mycobacterium tuberculosis lipoprotein conferring lysozyme resistance. Based on the presence of such domain, we hypothesized a role of this S. Typhimurium protein in PG metabolism. This protein, which we named ScwA for Salmonella cell wall-related regulator-A, controls positively the levels of the murein lytic transglycosylase MltD. In addition, the levels of other enzymes that cleave bonds in the PG lattice were affected in a mutant lacking ScwA, including a soluble lytic tranglycosylase (Slt), the amidase AmiC, and a few endo- and carboxypeptidases (NlpC, PBP4, and AmpH). The scwA gene has lower G+C content than the genomic average (43.1 vs. 52.2%), supporting acquisition by horizontal transfer. ScwA is located in the periplasm, stabilized by two disulfide bridges, produced preferentially in stationary phase and down-regulated following entry of the pathogen into eukaryotic cells. ScwA deficiency, however, results in a hypervirulent phenotype in the murine typhoid model. Based on these findings, we conclude that ScwA may be exploited by S. Typhimurium to ensure cell envelope homeostasis along the infection and to prevent host overt damage. This role could be accomplished by controlling the production or stability of a reduced number of peptidoglycan hydrolases whose activities result in the release of PG fragments.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/262324
url http://hdl.handle.net/10261/262324
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3389/fmicb.2021.633701
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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