title: Listeria monocytogenes CadC Regulates Cadmium Efflux and Fine-tunes Lipoprotein Localization to Escape the Host Immune Response and Promote Infection.
abstract: Listeria monocytogenes is a major intracellular human foodborne bacterial pathogen. We previously revealed L. monocytogenes cadC as highly expressed during mouse infection. Here we show that L. monocytogenes CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC but not CadA is required for L. monocytogenes infection in vivo. Interestingly, CadC also directly represses lspB, a gene encoding a lipoprotein signal peptidase whose expression appears detrimental for infection. lspB overexpression promotes the release of the LpeA lipoprotein to the extracellular medium, inducing tumor necrosis factor α and interleukin 6 expression, thus impairing L. monocytogenes survival in macrophages. We propose that L. monocytogenes uses CadC to repress lspB expression during infection to avoid LpeA exposure to the host immune system, diminishing inflammatory cytokine expression and promoting intramacrophagic survival and virulence. CadC appears as the first metal efflux pump regulator repurposed during infection to fine-tune lipoprotein processing and host responses.
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Pombinho
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Camejo
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Vieira
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Olga
authors.initials: O
authors.lastname: Reis
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Almeida
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Jorge Campos
authors.initials: JC
authors.lastname: Pinheiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sousa
authors.affiliation: Instituto de Investigação e Inovação em Saúde and.|Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: Didier
authors.initials: D
authors.lastname: Cabanes
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D008074:Lipoproteins / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010454:Peptide Termination Factors / Q000378:metabolism; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C080050:CadC protein, Bacteria; D008074:Lipoproteins; D010454:Peptide Termination Factors; C545356:PrfA protein, Listeria monocytogenes; D037521:Virulence Factors; D002104:Cadmium
keywords: CadAC; Listeria/virulence factor; gram-positive; host-response; pathogen.