{"id":10611,"date":"2020-11-24T10:33:00","date_gmt":"2020-11-24T10:33:00","guid":{"rendered":"https:\/\/mycor.iam.inrae.fr\/IAM\/?p=10611"},"modified":"2020-12-11T14:44:23","modified_gmt":"2020-12-11T14:44:23","slug":"phd-defense-matthieu-nicault","status":"publish","type":"post","link":"https:\/\/mycor.iam.inrae.fr\/IAM\/?p=10611","title":{"rendered":"PhD Defense: Matthieu Nicault"},"content":{"rendered":"

Matthieu Nicault soutiendra sa th\u00e8se, intitul\u00e9e \u00ab Prospection et induction de mol\u00e9cules anti-microbiennes par co-culture entre bact\u00e9ries (Streptomyces) et champignons (Basidiomyc\u00e8tes) \u00bb, le vendredi 27 Novembre 2020 \u00e0 14h en visioconf\u00e9rence sur TEAMS<\/a>.<\/p>\n

Ce travail de th\u00e8se a \u00e9t\u00e9 r\u00e9alis\u00e9 au sein des UMR DynAMic et IAM sous la direction de Cyril Bontemps, Eric Gelhaye et Pierre Leblond.<\/p>\n

\"\"<\/a><\/p>\n

Membres du Jury :<\/strong><\/p>\n

Rapporteurs :<\/strong><\/p>\n

Madame Jenny Renaut (responsable de plateforme \u00ab -omiques \u00bb, LIST, Luxembourg)<\/p>\n

Madame Marie-Jo\u00eblle Virolle (Directrice de recherche CNRS, Paris)<\/p>\n

Examinateurs :<\/strong><\/p>\n

Monsieur David Touboul (directeur de recherche CNRS, Paris)<\/p>\n

Madame M\u00e9lanie Morel-Rouhier (Professeure de l\u2019Universit\u00e9 de Lorraine, Nancy)<\/p>\n

Monsieur Cyril Bontemps (Maitre de conf\u00e9rences de l\u2019Universit\u00e9 de Lorraine\/Co-directeur de th\u00e8se – invit\u00e9)<\/p>\n

Monsieur Eric Gelhaye (Professeur de l\u2019Universit\u00e9 de Lorraine\/Co-directeur de th\u00e8se)<\/p>\n

Monsieur Pierre Leblond (Professeur de l\u2019Universit\u00e9 de Lorraine\/Directeur de th\u00e8se)<\/p>\n

R\u00e9sum\u00e9 de la th\u00e8se :<\/strong><\/p>\n

L\u2019\u00e9mergence de r\u00e9sistances multiples aux antibiotiques chez les micro-organismes pathog\u00e8nes constitue une menace importante en sant\u00e9 humaine. L\u2019identification de principes actifs nouveaux avec des cibles cellulaires et des m\u00e9canismes originaux est un besoin urgent et en ce sens les micro-organismes du sol (bact\u00e9ries et champignons) riches en mol\u00e9cules biologiques constituent un r\u00e9servoir d\u2019int\u00e9r\u00eat.<\/p>\n

Au cours de cette th\u00e8se, nous nous sommes int\u00e9ress\u00e9s \u00e0 des souches isol\u00e9es conjointement (communaut\u00e9) de Streptomyces, des bact\u00e9ries filamenteuses du sol produisant plus de la moiti\u00e9 des antibiotiques utilis\u00e9s en m\u00e9decine. Une analyse conjointe du m\u00e9tabolome et du g\u00e9nome de 8 souches (dont 5 ont \u00e9t\u00e9 s\u00e9quenc\u00e9s au cours de cette \u00e9tude) a montr\u00e9 une diversit\u00e9 importante des voies de biosynth\u00e8se de m\u00e9tabolites sp\u00e9cialis\u00e9s au sein de cette communaut\u00e9. Afin de stimuler l\u2019expression de nouvelles mol\u00e9cules cryptiques en conditions de laboratoire, la co-culture de ces Streptomyces et de champignons a \u00e9t\u00e9 r\u00e9alis\u00e9e. Un criblage de 64 co-cultures entre 8 souches de Streptomyces et 8 esp\u00e8ces de champignons Basidiomyc\u00e8tes a \u00e9t\u00e9 r\u00e9alis\u00e9 en suivant des activit\u00e9s antimicrobiennes, anti-inflammatoires et anti-oxydantes induites (c\u2019est-\u00e0-dire produites en co-culture mais pas dans les cultures seules des bact\u00e9ries et des champignons). Nos criblages ont r\u00e9v\u00e9l\u00e9 deux interactions prometteuses dont les produits ont \u00e9t\u00e9 analys\u00e9s par la combinaison d\u2019une approche m\u00e9tabolomique couplant chromatographie gazeuse, spectrom\u00e9trie de masse (GC-MS), chromatographie liquide et spectrom\u00e9trie de masse en tandem (LC-MS\/MS). Un fractionnement guid\u00e9 par l\u2019activit\u00e9 antimicrobienne a permis d\u2019identifier un ensemble de compos\u00e9s candidats en lien avec l\u2019activit\u00e9 antimicrobienne.<\/p>\n

En r\u00e9v\u00e9lant une grande variabilit\u00e9 des g\u00e8nes de biosynth\u00e8se de mol\u00e9cules biologiques, nos r\u00e9sultats ont permis dans un premier temps de circonscrire la communaut\u00e9 comme un cadre d\u2019\u00e9chantillonnage appropri\u00e9 pour rechercher des mol\u00e9cules biologiques d\u2019int\u00e9r\u00eat chez les Streptomyces. Ces g\u00e8nes \u00e9tant pour la plupart cryptiques en conditions de laboratoire, nous avons pu \u00e9galement souligner l\u2019int\u00e9r\u00eat de la co-culture comme stimulus biotique permettant leur production, en faisant une approche prometteuse en biotechnologie.<\/p>\n

Mots cl\u00e9s :<\/strong> G\u00e9nomique, M\u00e9tabolomique, Co-cultures, Streptomyces, Champignons, Basidiomyc\u00e8tes<\/p>\n

Abstract:<\/strong><\/p>\n

Prospecting and induction of anti-microbial molecules by co-culture between bacteria (Streptomyces) and fungi (Basidiomycetes)<\/p>\n

The emergence of multiple resistance to antibiotics in pathogenic microorganisms poses a significant threat to human health. The identification of new active ingredients with cellular targets and original mechanisms is an urgent need and in this sense soil microorganisms (bacteria and fungi) rich in biological molecules constitute a reservoir of interest.<\/p>\n

During this thesis, we were interested in jointly isolated strains (community) of Streptomyces, filamentous bacteria from the soil producing more than half of the antibiotics used in medicine. A joint analysis of the metabolome and the genome of 8 strains (5 of which were sequenced during this study) showed a significant diversity of the biosynthetic pathways of specialized metabolites within this community. In order to stimulate the expression of new cryptic molecules under laboratory conditions, the co-culture of these Streptomyces and fungi was performed. A screening of 64 co-cultures between 8 strains of Streptomyces and 8 species of Basidiomycetes fungi was performed by monitoring induced antimicrobial, anti-inflammatory and anti-oxidant activities (i.e. produced in co-culture but not in cultures only bacteria and fungi). Our screens revealed two promising interactions whose products were analyzed by the combination of a metabolomics approach coupling gas chromatography, mass spectrometry (GC-MS), liquid chromatography and tandem mass spectrometry (LC-MS \/ MS). Antimicrobial activity-guided fractionation has identified a set of candidate compounds related to antimicrobial activity.<\/p>\n

By revealing a large variability of genes for the biosynthesis of biological molecules, our results first allowed us to define the community as an appropriate sampling framework to search for biological molecules of interest in Streptomyces. As these genes are mostly cryptic under laboratory conditions, we were also able to underline the interest of co-culture as a biotic stimulus allowing their production, making it a promising approach in biotechnology.<\/p>\n

Keywords:<\/strong> Genomics, Metabolomics, Co-cultures, Streptomyces, Mushrooms, Basidiomycetes<\/p>\n","protected":false},"excerpt":{"rendered":"

Matthieu Nicault soutiendra sa th\u00e8se, intitul\u00e9e \u00ab Prospection et induction de mol\u00e9cules anti-microbiennes par co-culture entre bact\u00e9ries (Streptomyces) et champignons (Basidiomyc\u00e8tes) \u00bb, le vendredi 27 Novembre 2020 \u00e0 14h en visioconf\u00e9rence sur TEAMS. Ce travail de th\u00e8se a \u00e9t\u00e9 r\u00e9alis\u00e9 … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8],"tags":[],"class_list":["post-10611","post","type-post","status-publish","format-standard","hentry","category-thesis"],"_links":{"self":[{"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=\/wp\/v2\/posts\/10611","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=10611"}],"version-history":[{"count":0,"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=\/wp\/v2\/posts\/10611\/revisions"}],"wp:attachment":[{"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=10611"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=10611"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mycor.iam.inrae.fr\/IAM\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=10611"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}