Screening the Sec proteins in the core genome of the gut
Date de début
Date de fin
Sylvain Marthey et Gwenaëlle André


Contrat de recherche

The intestinal tract is a nutrient-rich environment containing up to 1014 microorganisms. The symbiotic interactions between the gut microbiota and the host results from a long coevolution. This mutualism allows energy and nutritional benefices for each part, and leads to homeostasis. The crosstalk between bacteria and the host is dominated by the importance of sensing the metabolic environment as well as the immune state of the host, and adapt to it accordingly. Also, emerges the idea that the host perceives the metabolites produced by the bacteria, often similar to its own metabolites, and possibly senses the physiological state of a bacteria. Despite being interesting, this hypothesis deserves more documentation. From the bacteria signaling, we and collaborators evidenced that intra-cellular pathogens have developed finely regulated signaling pathways in glucose metabolism or in phosphatidyl-inositol phosphates recycling. Those proteins refer to Ser/Thr/Tyr kinases or secreted Ser/Thr/Tyr phosphatases. We suspect those proteins to be largely present in the gut, where they could associate multi-domain organizations with exquisite specificity, targeting nutrient acquisition or immunity pathways. Still, an open question is the mode of secretion of those phosphatases as their substrates are mainly proteins of the host. How and in which state do they exit from their bacterial cell to export and interact with the host proteins? As such, they constitute exciting targets to be screened and analyzed. To that end, we are currently setting up a suite of innovative bioinformatics tools, combining data screening with interactive visualization. In the present project, the student will screen in silico the core gut composed of 58 most prevalent bacteria to document the co-occurrence of the operons coding for the secretion system such as Tat, SecA1-A2 and ESX/Type VII. Indeed, the prevalence, distribution and diversity of protein Ser/Thr/Tyr phosphatases, were our prime focus and have been computed. Their analysis is in progress. Also, during his. her internship, the student will be in charge of modeling the structure and characterizing the sequence/structure/function of selected phosphatases, and secretion system chosen upon structural and biological relevance. In fine, we aim to assemble all these data in order to gain insights about the synteny of the system and their capacity to enter a host cell and regulate homeostasis.

Niveau/diplôme (pour les stages)