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J Infect Dis. 2017 May 1;215(9):1468-1479. doi: 10.1093/infdis/jix118.

Listeria monocytogenes CadC Regulates Cadmium Efflux and Fine-tunes Lipoprotein Localization to Escape the Host Immune Response and Promote Infection.

Pombinho R1,2,3, Camejo A1,2,3, Vieira A1,3, Reis O1,2,3, Carvalho F1,2,3, Almeida MT1,2,3, Pinheiro JC1,2,3, Sousa S1,3, Cabanes D1,3.

Author information

1
Instituto de Investigação e Inovação em Saúde and.
2
Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.
3
Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular, Porto, Portugal.

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.

KEYWORDS:

CadAC; Listeria/virulence factor; gram-positive; host-response; pathogen.

PMID:
28368435
DOI:
10.1093/infdis/jix118
[Indexed for MEDLINE]

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