Arnaud FIRON - Vendredi 10 novembre 2017 14h
Auditorium - Bât. 442 - Séminaire Micalis
Cyclic di-AMP in bacterial physiologyand host interaction
Institut Pasteur, Unité Biologie des Bactéries Pathogènes à Gram-positif, CNRS URL3526, Paris
Cyclic di-AMP (c-di-AMP) is a conserved bacterial metabolite and an inflammatory ligand. Inside bacteria, c-di-AMP homeostasis is necessary to sustain growth by acting as a secondary messenger to control critical cellular functions. During infections, c-di-AMP is release outside bacteria and is recognized by host cells to trigger an innate immune response, leading primary to type I interferon (IFN) production.
We study this c-di-AMP dual function, necessary for bacterial growth but potentially leading to a detrimental innate response, inStreptococcus agalactiae (also known as GBS), the most frequent cause of bacterial invasive infections in neonates. We have found that GBS limits the immune response by degrading its own c-di-AMP released into infected cells. This enzymatic activity is due to a cell-wall anchor nucleotidase which limits the activation of the host cGAS-STING signaling axis, improving bacterial colonization of the host.
We next characterized the essential function of c-di-AMP for GBS physiology. We have found that this “essential” function is dispensable under specific growth condition. We have characterized the genetic pathways dependent on c-di-AMP by analyzing suppressive mutations and direct c-di-AMP binding proteins. Overall, c-di-AMP is a conserved signaling molecule essential to maintain osmotic homeostasis, host cell have c-di-AMP sensors to monitor infection, and bacterial manipulation of the host response to c-di-AMP might be a common mechanism to exacerbate infection.
Vendredi 10 novembre 2017
Auditorium - Bât. 442
INRA, Jouy en Josas
Invité par Delphine Lechardeur