|Invasive Bacterial Infections|
|HEAD||Dr Muhamed-Kheir Taha / firstname.lastname@example.org|
|MEMBERS||Dr. Aude ANTIGNAC, Dr. Ala-Eddine DEGHMANE , Hela EL KAFSI , Dario GIORGINI , Eva HONG, Dr. Mireille LARRIBE, Jamila NAIT-ABDALLAH, Corinne RUCKLY, Marek SZATANIK, Dr. Muhamed-Kheir TAHA, Dr. Frédéric Veyrier, Pascale VIENNE
Our main objective is to study Neisseria meningitidis/host interactions and the balance between non-offending commensality (nasopharyngeal carriage of this bacterium) and devastating invasive infections (mainly septicaemia and meningitis). We therefore developed a relevant humanized mouse models using transgenic mice expressing the human transferrin (hTf). This model allowed studying the virulence of different meningococcal isolates and permitted to characterize hyperinvasive genotypes. We also analyzed the cytotoxicity of disease- or asymptomatic carriage-associated meningococcal isolates towards infected epithelial human cells. We were able to determine the nature of cell death resulting from this cytotoxicity (apoptosis).In particular, TNF-α and its receptor TNF-RI were shown to be involved I nthe induction of apoptosis. Indeed, TNF-αsignals through two distinct receptors: TNF-RI and TNF-RII. Binding of TNF-αto TNF-RI results in activation of the inhibitor of κB kinase (IKK) andc-Jun N-terminal kinase (JNK) pathways. These two pathways involve a complex network of kinases, which are co-ordinatelyregulated and respectively important in survival and death.
Our unit >also harbors the National Centre of Reference for meningococci. Our work on the induction of apoptosis and inflammation by N. meningitis in infected cells allowed us to detect the emergence of a new hyperinvasive serogroup C clone that was involved is several outbreaks in France. These findings contributed to the decision of the health authorities to introduce routine vaccination against the disease in France in 2010.
Keywords: Meningitis, Host-bacteria interaction, inflammation, molecular epidemiology, vaccine
1-Deghmane, A.E., Veckerle, C., Giorgini, D., Hong, E., Ruckly, C., and Taha, M.K. (2009) Differential modulation of TNF-alpha-induced apoptosis by Neisseria meningitidis. PLoS Pathog5: e1000405. (PMID 19412525)
2-Rameix-Welti, M.A., Zarantonelli, M.L., Giorgini, D., Ruckly, C., Marasescu, M., van der Werf, S., Alonso, J.M., Naffakh, N., and Taha, M.K. (2009) Influenza A virus neuraminidase enhances meningococcal adhesion to epithelial cells through interaction with sialic acid-containing meningococcal capsules. Infect Immun77: 3588-3595. (PMID 19528219)
3-Deghmane, A.E., Parent du Chatelet, I., Szatanik, M., Hong, E., Ruckly, C., Giorgini, D., Levy-Bruhl, D., Alonso, J.M., and Taha, M.K. (2010) Emergence of new virulent Neisseria meningitidis serogroup C sequence type 11 isolates in France. J Infect Dis202: 247-250. (PMID 20515410)
4-Murphy, E., Andrew, L., Lee, K.L., Dilts, D.A., Nunez, L., Fink, P.S., Ambrose, K., Borrow, R., Findlow, J., Taha, M.K., Deghmane, A.E., Kriz, P., Musilek, M., Kalmusova, J., Caugant, D.A., Alvestad, T., Mayer, L.W., Sacchi, C.T., Wang, X., Martin, D., von Gottberg, A., du Plessis, M., Klugman, K.P., Anderson, A.S., Jansen, K.U., Zlotnick, G.W., and Hoiseth, S.K. (2009) Sequence Diversity of the Factor H Binding Protein Vaccine Candidate in Epidemiologically Relevant Strains of Serogroup B Neisseria meningitidis. J Infect Dis 200: 379-389.
5-Taha, M.K., Thulin Hedberg, S., Szatanik, M., Hong, E., Ruckly, C., Abad, R., Bertrand, S., Carion, F., Claus, H., Corso, A., Enriquez, R., Heuberger, S., Hryniewicz, W., Jolley, K.A., Kriz, P., Mollerach, M., Musilek, M., Neri, A., Olcen, P., Pana, M., Skoczynska, A., Sorhouet Pereira, C., Stefanelli, P., Tzanakaki, G., Unemo, M., Vazquez, J.A., Vogel, U., and Wasko, I. (2010) Multicenter Study for Defining the Breakpoint for Rifampin Resistance in Neisseria meningitidisby rpoB Sequencing. >Antimicrob Agents Chemother 54: 3651-3658. (PMID 20606072)
Activity Reports 2010 - Institut Pasteur
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