title: Listeria monocytogenes encodes a functional ESX-1 secretion system whose expression is detrimental to in vivo infection.
abstract: Bacterial pathogenicity deeply depends on the ability to secrete virulence factors that bind specific targets on host cells and manipulate host responses. The Gram-positive bacterium Listeria monocytogenes is a human foodborne pathogen that remains a serious public health concern. To transport proteins across its cell envelope, this facultative intracellular pathogen engages a set of specialized secretion systems. Here we show that L. monocytogenes EGDe uses a specialized secretion system, named ESX-1, to secrete EsxA, a homolog of the virulence determinants ESAT-6 and EsxA of Mycobacterium tuberculosis and Staphylococcus aureus, respectively. Our data show that the L. monocytogenes ESX-1 secretion system and its substrates are dispensable for bacterial invasion and intracellular multiplication in eukaryotic cell lines. Surprisingly, we found that the EssC-dependent secretion of EsxA has a detrimental effect on L. monocytogenes in vivo infection.
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.|c Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto , Porto , Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pinheiro
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.|c Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto , Porto , Portugal.
authors.forename: Olga
authors.initials: O
authors.lastname: Reis
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Vieira
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.
authors.forename: Ines M
authors.initials: IM
authors.lastname: Moura
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.|d Laboratório de Saúde Pública , Faculdade de Saúde Pública, Universidade de São Paulo , São Paulo , Brazil.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zanolli Moreno
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.|c Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto , Porto , Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: e Centro Nacional de Biotecnología-CSIC (CNB-CSIC) , Madrid , Spain.|f Departamento de Biología Molecular , Universidad Autónoma de Madrid, Centro de Biología Molecular "Severo Ochoa" (CBMSO-CSIC) , Madrid , Spain.
authors.forename: M Graciela
authors.initials: MG
authors.lastname: Pucciarelli
authors.affiliation: e Centro Nacional de Biotecnología-CSIC (CNB-CSIC) , Madrid , Spain.
authors.forename: Francisco
authors.identifier: 0000-0002-4120-0530
authors.initials: F
authors.lastname: García-Del Portillo
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.
authors.forename: Sandra
authors.identifier: 0000-0001-8578-0461
authors.initials: S
authors.lastname: Sousa
authors.affiliation: a Instituto de Investigação e Inovação em Saúde - i3S, Universidade do Porto , Porto , Portugal.|b Group of Molecular Microbiology , Instituto de Biologia Molecular e Celular - IBMC , Porto , Portugal.
authors.forename: Didier
authors.identifier: 0000-0002-4001-1332
authors.initials: D
authors.lastname: Cabanes
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D013211:Staphylococcus aureus / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D037521:Virulence Factors
keywords: ESAT-6; ESX-1 secretion system; EsxA; Listeria monocytogenes; Type VII secretion system