title: A novel peptidoglycan D,L-endopeptidase induced by Salmonella inside eukaryotic cells contributes to virulence.
abstract: Bacteria remodel peptidoglycan structure in response to environmental changes. Many enzymes are involved in peptidoglycan metabolism; however, little is known about their responsiveness in a defined environment or the modes they assist bacteria to adapt to new niches. Here, we focused in peptidoglycan enzymes that intracellular bacterial pathogens use inside eukaryotic cells. We identified a peptidoglycan enzyme induced by Salmonella enterica serovar Typhimurium in fibroblasts and epithelial cells. This enzyme, which shows γ-D-glutamyl-meso-diaminopimelic acid D,L-endopeptidase activity, is also produced by the pathogen in media with limited nutrients and in resting conditions. The enzyme, termed EcgA for endopeptidase responding to cessation of growth', is encoded in a S. Typhimurium genomic island absent in Escherichia coli. EcgA production is strictly dependent on the virulence regulator PhoP in extra- and intracellular environments. Consistent to this regulation, a mutant lacking EcgA is attenuated in the mouse typhoid model. These findings suggest that specialised peptidoglycan enzymes, such as EcgA, might facilitate Salmonella adaptation to the intracellular lifestyle. Moreover, they indicate that readjustment of peptidoglycan metabolism inside the eukaryotic cell is essential for host colonisation.
authors.affiliation: Laboratory of Intracellular Bacterial Pathogens, Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: Gadea
authors.initials: G
authors.lastname: Rico-Pérez
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Rosario, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pezza
authors.affiliation: Laboratory of Intracellular Bacterial Pathogens, Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.|Centro de Biología Molecular 'Severo Ochoa' (CBMSO-CSIC), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: M Graciela
authors.initials: MG
authors.lastname: Pucciarelli
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (CBMSO-CSIC), Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: de Pedro
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Rosario, Argentina.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Soncini
authors.affiliation: Laboratory of Intracellular Bacterial Pathogens, Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-del Portillo
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000378:metabolism*; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D010457:Peptidoglycan; D010450:Endopeptidases