Laboratoire de Chimie Bactérienne UMR 7283

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5 octobre 2017: 1 événement


  • Séminaire LCB

    Jeudi 5 octobre 14:00-15:00 - Elsa Germain

    Séminaire LCB

    Résumé : "Recurrent infections are often caused by bacteria that are sensitive to commonly used antibiotics. One reason for this recalcitrance is that bacteria form persister cells that are multidrug tolerant. We are focusing on the pivotal role of the general bacterial stress response, known as “the stringent response” in this phenomenon. Indeed, stochastic variation of the stringent response regulator (p)ppGpp triggers persister cell formation1 ;2. This response is controlled by two proteins in E.coli called RelA and SpoT that encode respectively for ppGpp synthetases I and II (PSI and PSII)3. SpoT has both ppGpp hydrolytic and synthetic activities, whereas RelA lacks ppGpp hydrolytic activity. We recently observed that the ppGpp synthetase of SpoT is responsible for persister cell formation in E. coli. While conditions that trigger SpoT PSII activity have been found (fatty acid, carbone phosphate and iron starvation), the molecular mechanisms regulating SpoT activities are poorly understood. Indeed, only one regulator of SpoT activity has been described : SpoT senses fatty acid starvation by direct interact with Acyl Carrier Protein4.
    Here by using a genetic screen approach we identify a new partner required for the activation of the SpoT PSII activity. Indeed overproduction of YtfK, a protein of unknown function stimulates SpoT dependent ppGpp synthesis. This response is mediated by the physical interaction between YtfK and SpoT in vivo. This interaction seems specific to SpoT since YtfK does not interact with the homologous RelA. Moreover by using truncated SpoT fusion proteins, we demonstrate further that YtfK binds to the catalytic domain of SpoT. Finally we observed that deletion of ytfK abolishes the accumulation of ppGpp observed in response to phosphate and fatty acid starvation.
    This work highlights the important role of YtfK in stimulating (p)ppGpp accumulation in response to metabolic cues and potentially in controlling bacterial multigrug tolerance and stress response."

    Lieu : Salle Georges Morin

    En savoir plus : Séminaire LCB

5 octobre 2017: 1 événement

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