instituto de biologia molecular e celular | institute for molecular and cell biology
Previous research results
Listeria monocytogenes is an intracellular human food-borne pathogen that causes listeriosis, an infection characterized by gastroenteritis, meningitis, encephalitis and maternofetal infections. L. monocytogenes enters the host via the ingestion of contaminated foods, invades the intestine, translocates to mesenteric lymph nodes and spreads to the liver, spleen, brain and to the placenta. During infection, Listeria has the ability to cross the intestinal, the blood-brain and the placental barriers, entering, surviving and multiplying inside phagocytic and non-phagocytic cells. L. monocytogenes thus emerged as an exceptional model to address the different facets of host-pathogen interactions. Our research is focused on the identification and analysis of virulence mechanisms used by L. monocytogenes to enter, survive and proliferate into its host.
We have identified and characterized several Listeria factors crucial for virulence and involved in cell adhesion, invasion or resistance to host defences. We performed the first genome-wide expression analysis of a bacterial pathogen in deep infected mouse organs, revealing how Listeria adapts to host conditions, activates virulence mechanisms and subverts host defence functions. We also identified new host factors hijacked by Listeria to promote infection, performed the molecular characterization of the interaction between Listeria virulence factors and host receptors, and deciphered signalling cascades downstream these interactions.
IMAGE: Listeria monocytogenes infecting human cells. Bacteria are visualized in red, cell nuclei in blue and cellular actin in green.
Future research goals
Our current and future objectives include not only the description of new aspects of the Listeria-host interaction, but also the involvement of newly identified proteins and pathways in the infectious process of other pathogens.
We are characterizing new Listeria virulence factors that we identified by in vivo transcriptomics. In particular, we try to assess the role of wall teichoic acids glycosylation and cadmium efflux system in Listeria virulence.
Host phosphorylation cascades are preferential targets of infecting bacteria. We recently identified two new cytoskeletal proteins differentially phosphorylated in response to Listeria uptake. Our goal is to address the role of these phosphorylations in the infectious process and also in general cellular processes.
We will also investigate the possible interplay between Listeria and the host cell cycle, and address the role of this crosstalk in the establishment and progression of cellular infection.
As different pathogens often hijack same signalling pathways, we will investigate the involvement of the newly identified proteins/pathways in the infectious processes of other human pathogens, as pathogenic E. coli and Yersinia.
Lebreton A, Lakisic G, Job V, Fritsch L, Tham TN, Camejo A, Matteï PJ, Regnault B, Nahori MA, Cabanes D, Gautreau A, Ait-Si-Ali S, Dessen A, Cossart P, Bierne H.. A Bacterial Protein Targets the BAHD1 Chromatin Complex to Stimulate Type III Interferon Response. Science 2011 , 331(6022):1319-21.
Reis O, Sousa S, Camejo A, Villiers V, Gouin E, Cossart P, et al. LapB, a novel Listeria monocytogenes LPXTG surface adhesin, required for entry into eukaryotic cells and virulence. J Infect Dis 2010; 202:551-62.
Camejo A, Buchrieser C, Couvé E, Carvalho F, Reis O, Ferreira P, Sousa S, Cossart P and Cabanes D. In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection. PloS Pathogens, 2009, 5(5):e1000449.
Sousa S, Cabanes D, Bougnères L, Lecuit M, Sansonetti P, Tran-Van-Nhieu G and Cossart P. Src, cortactin and Arp2/3 complex are required for E-cadherin-mediated internalization of Listeria into cells. Cellular Microbiology, 2007 9(11):2629-2643.
Boneca I, Dussurget O, Cabanes D, Nahori MA, Sousa S, Lecuit M, Psylinakis E, Bouriotis V, Hugot JP, Giovannini M, Coyle A, Bertin J, Namane A, Rousselle JC, Cayet N, Prévost MC, Balloy V, Chignard M, Philpott D, Cossart P, Girardin S. A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system. PNAS, 2007 104(3):9997-1002.
Sousa S, Cabanes D, Archambaud C, Colland F, Lemichez E, Popoff M, Boisson-Dupuis S, Gouin E, Lecuit M, Legrain P and Cossart P. ARHGAP10 is necessary for alpha-catenin recruitment at adherens junctions and for Listeria invasion. Nature Cell Biology, 2005 7(10):954-60.
Miguel Fernandes Cunha, Paulo
Ribeiro Mesquita, Francisco
Teixeira da Costa, Ana Catarina
Cruz, Rui Filipe
Pinheiro, Jorge Nuno
Pombinho, Rita Pereira
Moranguinho Bastardo Moura, Inês
Patrícia Fernandes de Brito, Cláudia
Malheiro, Teresa Almeida