1. Virulence gene repression promotes Listeria monocytogenes systemic infection
- Author
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Didier Cabanes, Ana Camejo, Cristel Archambaud, Pascale Cossart, Rita Pombinho, Sandra Maria Zákia Lian Sousa, Ana Rita Vieira, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Group of Molecular Microbiology, Instituto de Biologia Molecular e Celular (IBMC), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cell Biology of Bacterial Infections, FEDER - Fundo Europeu de Desenvolvimento Regional funds through the NORTE 2020 - Norte Portugal Regional Operational Programme, Portugal 2020 Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior NORTE-01-0145-FEDER-030020 PTDC/SAU-INF/30020/2017FCT through FCT/MEC - QREN SFRH/BD/89542/2012SFRH/BD/29314/2006POPH (Programa Operacional Potencial Humano) FCT Investigator program (COMPETE) FCT Investigator program (POPH) FCT Investigator program (FCT), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Universidade do Porto [Porto], Instituto deBiologia Molecular e Celular (IBMC), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), FEDER - Fundo Europeu de Desenvolvimento Regional funds through the NORTE 2020 - Norte Portugal Regional Operational Programme, Portugal 2020 Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior NORTE-01-0145-FEDER-030020 PTDC/SAU-INF/30020/2017European Research Council (ERC) BacCellEpi 670823FCT through FCT/MEC - QREN SFRH/BD/89542/2012 SFRH/BD/29314/2006POPH (Programa Operacional Potencial Humano) FCT Investigator program (COMPETE) FCT Investigator program (POPH) FCT Investigator program (FCT), Universidade do Porto, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lallemant, Christopher, Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID, and Instituto de Investigação e Inovação em Saúde
- Subjects
0301 basic medicine ,Listeria monocytogenes / physiology ,medicine.disease_cause ,Mice ,0302 clinical medicine ,Gram-positive pathogen ,Listeriosis ,Regulation of gene expression ,Listeria monocytogenes / genetics ,Virulence ,Gastroenterology ,Cholic Acid / metabolism ,Virulence Factors / metabolism ,Bile Acids and Salts / metabolism ,3. Good health ,Listeria monocytogenes / drug effects ,Infectious Diseases ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,030211 gastroenterology & hepatology ,Female ,Listeria monocytogenes / pathogenicity ,Efflux ,Infection ,Microbiology (medical) ,Virulence Factors / genetics ,Bacterial Proteins / genetics ,MESH: Listeria ,Bile-salt hydrolase ,Gene regulation ,Listeria ,Virulence Factors ,Gastrointestinal Tract / microbiology ,Repressor ,Cholic Acid ,Biology ,Microbiology ,Regulon ,Amidohydrolases ,Bile Acids and Salts ,03 medical and health sciences ,Listeria monocytogenes ,Bacterial Proteins ,Virulence / genetics ,Amidohydrolases / genetics ,Bacterial Proteins / metabolism ,Drug Resistance, Bacterial ,medicine ,Animals ,Psychological repression ,Gene ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Bile Acids and Salts / pharmacology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Gene Expression Regulation, Bacterial ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Gastrointestinal Tract ,Mice, Inbred C57BL ,030104 developmental biology ,Genes, Bacterial ,Research Paper/Report ,Amidohydrolases / metabolismo ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Genes, MDR ,Listeriosis / microbiology - Abstract
The capacity of bacterial pathogens to infect their hosts depends on the tight spatiotemporal regulation of virulence genes. The Listeria monocytogenes (Lm) metal efflux pump repressor CadC is highly expressed during late infection stages, modulating lipoprotein processing and host immune response. Here we investigate the potential of CadC as broad repressor of virulence genes. We show that CadC represses the expression of the bile salt hydrolase impairing Lm resistance to bile. During late infection, in absence of CadC-dependent repression, the constitutive bile salt hydrolase expression induces the overexpression of the cholic acid efflux pump MdrT that is unfavorable to Lm virulence. We establish the CadC regulon and show that CadC represses additional virulence factors activated by sB during colonization of the intestinal lumen. CadC is thus a general repressor that promotes Lm virulence by down-regulating, at late infection stages, genes required for survival in the gastrointestinal tract. This demonstrates for the first time how bacterial pathogens can repurpose regulators to spatiotemporally repress virulence genes and optimize their infectious capacity. This work was supported by grants to DC (FEDER - Fundo Europeu de Desenvolvimento Regional funds through the NORTE 2020 - Norte Portugal Regional Operational Programme, Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project NORTE-01-0145-FEDER-030020 PTDC/SAU-INF/30020/2017); to PC (European Research Council - ERC - Advanced Grant BacCellEpi 670823). R.P. and A.C. received an FCT Doctoral Fellowship (SFRH/BD/89542/2012, SFRH/BD/29314/2006) through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH and FCT).
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- 2020
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