Where Ideas grow
Molecular Microbiology

ABOUT

We investigate new molecular and cellular facets of host-pathogen interactions using Listeria monocytogenes (Lm) as a model organism of intracellular parasitism for the design of new therapeutic strategies.

Using in vitro and in vivo experimental models, we aim to 1- decipher Lm virulence mechanisms deployed to adhere, invade, survive and multiply within the host, and 2- unravel the role of host cytoskeleton components in the establishment of cellular infection.

 

RESEARCH

Listeria monocytogenes (Lm) is a human bacterial food-borne pathogen that is the most frequent cause of death due to the consumption of contaminated food in Europe. We have been studying the Lm infectious process for the last 15 years and we greatly contributed to its current understanding, identifying and characterizing a large number of bacterial and host factors involved in Lm infection.

We performed the first transcriptome of bacteria growing inside mouse organs, revealing how Lm adapts its genome expression for virulence and identifying novel virulence factors. We showed how Lm glycosylates its wall teichoic acids to promote resistance to antimicrobial peptides. We demonstrated that Lm induces host DNA damage and delays the host cell cycle to promote infection. We identified the ER chaperone Gp96 as a Lm cell surface receptor involved in infection, showed how Src-dependent tyrosine phosphorylation of myosin-IIA restricts Lm cell infection, and revealed how Gp96 coordinates actomyosin dynamics and plasma membrane blebbing, protecting the host against bacterial pore-forming toxins.

 

Collaborations
J. Leong, Tufts University-Boston
D. Holden, Imperial College-London
P. Cossart, Institut Pasteur-Paris
F. Garcia-del Portillo, CSIC-Madrid
C. Arraiano, ITQB-Oeiras
S. Raposo Filipe, ITQB-Oeiras
S. Mostowy, Imperial College-London
J. Sellers, NIH-NHLBI- Bethesda, USA
E. De La Cruz, Yale University- USA
B. Wollscheid, ETH-Zurich

 

Current Grants
- Infect-ERA/0001/2013 – PROANTILIS - Subversive pro and anti-inflammation tradeoffs promote infection by Listeria monocytogenes. (FCT)
- NORTE-01-0145-FEDER-000012 – Structured Program on Bioengineered Therapies for Infectious Diseases and Tissue Regeneration. (Norte2020)
- H2020-MSCA-IF-2015 a-sign – Cyclic nucleotide signaling in the human pathogen Listeria monocytogenes. (European Commission)

Selected Publications
MouR controls the expression of the Listeria monocytogenes Agr system and mediates virulence. Nucleic Acids Research46(18):9338-9352, 2018. [Journal: Article] [CI: 1]
DOI: 10.1093/nar/gky624 SCOPUS: 85054896319

Stathmin recruits tubulin to Listeria monocytogenes-induced actin comets and promotes bacterial dissemination. Cellular and Molecular Life Sciences:, 2018. [Journal: Article in Press] [IF: 6,7 (*)]
DOI: 10.1007/s00018-018-2977-7 SCOPUS: 85057542589

Epithelial keratins modulate cMet expression and signaling and promote InlB-mediated Listeria monocytogenes infection of HeLa cells. Frontiers in Cellular and Infection Microbiology8(MAY):, 2018. [Journal: Article] [CI: 1] [IF: 3,5 (*)]
DOI: 10.3389/fcimb.2018.00146 SCOPUS: 85046878080

l-Rhamnosylation of wall teichoic acids promotes efficient surface association of Listeria monocytogenes virulence factors InlB and Ami through interaction with GW domains. Environmental Microbiology20(11):3941-3951, 2018. [Journal: Article] [IF: 5 (*)]
DOI: 10.1111/1462-2920.14351 SCOPUS: 85056596957

Listeria monocytogenes CadC regulates cadmium efflux and fine-tunes lipoprotein localization to escape the host immune response and promote infection. Journal of Infectious Diseases215(9):1468-1479, 2017. [Journal: Article] [CI: 3] [IF: 5,2]
DOI: 10.1093/infdis/jix118 SCOPUS: 85021919420

Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins. EMBO Reports18(2):303-318, 2017. [Journal: Article] [CI: 5] [IF: 8,7]
DOI: 10.15252/embr.201642833 SCOPUS: 85007487818

L-Rhamnosylation of Listeria monocytogenes Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane. PLoS Pathogens11(5):, 2015. [Journal: Article] [CI: 20] [IF: 7]
DOI: 10.1371/journal.ppat.1004919 SCOPUS: 84930354332

Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection. Cell Cycle13(6):928-940, 2014. [Journal: Article] [CI: 14] [IF: 4,6]
DOI: 10.4161/cc.27780 SCOPUS: 84897994129

A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science331(6022):1319-1321, 2011. [Journal: Article] [CI: 91] [IF: 31,2]
DOI: 10.1126/science.1200120 SCOPUS: 79952515250

In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection. PLoS Pathogens5(5):, 2009. [Journal: Article] [CI: 127] [IF: 9]
DOI: 10.1371/journal.ppat.1000449 SCOPUS: 67249147690