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Miguel A Valvano


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									                                Institut de Recherches en Technologies
                                  et Sciences pour le Vivant (iRTSV)

                                            Séminaire iRTSV

                                Jeudi 13 mars 2008 à 9h
                                            Salle séminaire C3-104
                                    CEA – 17 rue des Martyrs – Grenoble

                                         Miguel A Valvano
Department of Microbiology and Immunology, University of Western Ontario,

   Burkholderia cenocepacia, an opportunistic pathogen with
                         many faces

Improvements in the treatment of genetic diseases, cancer, and organ transplantation have resulted in an
increased incidence of immunosuppression and the rise of opportunistic infections. The ability to persist and
adapt to several different niches, including host cells and tissues, is a common characteristic of opportunistic
bacteria. Adaptability is also reflected in the contrasting outcomes produced from the bacterial-host interactions
at the various niches where these microorganisms are found, as they can establish either beneficial or
pathogenic associations. The Burkholderia cepacia complex (Bcc), a group of closely related Burkholderia
species, is a good example of bacterial opportunism and adaptability. Bcc have emerged as multi-drug resistant
nosocomial pathogens in immunocompromised patients, particularly in those with chronic granulomatous
diseases and cystic fibrosis. Bcc strains possess an extraordinary ability to resist antimicrobial peptides and they
can survive intracellularly. Previous work in our laboratory has shown that Bcc isolates can persist in
membrane-bound vacuoles within phagocytic cells without bacterial replication, but the detailed mechanism of
bacterial persistence is unknown. I will discuss current work in our laboratory showing that Bcc bacteria can
survive intracellularly by delaying the maturation of the phagosome and phagolysosomal fusion. I will also
discuss the role of bacterial antioxidant defenses and resistance to antimicrobial peptides in promoting survival
and persistence of Bcc strains within cells and host tissues. In particular, I will present evidence suggesting a
two-tier hypothesis to explain the increased resistance of these bacteria to antimicrobial peptides. This
hypothesis supports a role for the lipopolysaccharide and a unique outer membrane to provide and
impermeability barrier, thus preventing access of the peptides to plasma membrane and intracellular targets. I
will show recent data on the characterization of a type VI secretion system and its impact on biofilm formation
and intracellular survival of B. cenocepacia.

                                                                                                       Hôte : iRTSV/LBBSI

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                                           Direction des Sciences du Vivant
                       Institut de Recherches en Technologies et Sciences pour le Vivant - iRTSV
                                         CEA - 17 rue des Martyrs - 38054 Grenoble cedex 9

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