In Vivo Transcriptional Profiling of Listeria monocytogenes and Mutagenesis Identify New Virulence Factors Involved in Infection

PLoS Pathogens

Ana Camejo¹  Pierre Ferreira¹  Sandra Sousa¹  Olga Reis¹  Filipe Carvalho¹  Didier Cabanes²  Carmen Buchrieser³  Elisabeth Couvé⁴  Pascale Cossart⁵ 

[1] IBMC - Instituto de Biologia Molecular e Celular, Group of Molecular Microbiology, Universidade do Porto, Porto, Portugal;Inserm U604, Paris, France;Institut Pasteur, UP Biologie des Bactéries Intracellulaires and CNRS URA 2171, Paris, France;Institut Pasteur, Unité Génétique des Génomes Bactériens CNRS URA 2171, Paris, France;Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France

关键词: Gene regulation;    Listeria monocytogenes;    Listeria;    Gene expression;    Virulence factors;    Spleen;    Regulator genes;    Mammalian genomics;   

DOI  :  10.1371/journal.ppat.1000449

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Listeria monocytogenes is a human intracellular pathogen able to colonize host tissues after ingestion of contaminated food, causing severe invasive infections. In order to gain a better understanding of the nature of host–pathogen interactions, we studied the L. monocytogenes genome expression during mouse infection. In the spleen of infected mice, ≈20% of the Listeria genome is differentially expressed, essentially through gene activation, as compared to exponential growth in rich broth medium. Data presented here show that, during infection, Listeria is in an active multiplication phase, as revealed by the high expression of genes involved in replication, cell division and multiplication. In vivo bacterial growth requires increased expression of genes involved in adaptation of the bacterial metabolism and stress responses, in particular to oxidative stress. Listeria interaction with its host induces cell wall metabolism and surface expression of virulence factors. During infection, L. monocytogenes also activates subversion mechanisms of host defenses, including resistance to cationic peptides, peptidoglycan modifications and release of muramyl peptides. We show that the in vivo differential expression of the Listeria genome is coordinated by a complex regulatory network, with a central role for the PrfA-SigB interplay. In particular, L. monocytogenes up regulates in vivo the two major virulence regulators, PrfA and VirR, and their downstream effectors. Mutagenesis of in vivo induced genes allowed the identification of novel L. monocytogenes virulence factors, including an LPXTG surface protein, suggesting a role for S-layer glycoproteins and for cadmium efflux system in Listeria virulence.

【 授权许可】

CC BY