Thèse Isite - Mécanismes Écologique et Moléculaire de Communautés Microbiennes Produisant des Biomolécules Présentant une Activité Anti-Listeria Monocytogenes Augmentée H/F

Doctorat.Gouv.Fr

Établissement : Université de Lorraine École doctorale : SIReNa - SCIENCE ET INGENIERIE DES RESSOURCES NATURELLES Laboratoire de recherche : LIBIO - Laboratoire d'Ingénierie des Biomolécules Direction de la thèse : Frédéric BORGES ORCID 0000000261595509 Début de la thèse : 2026-10-01 Date limite de candidature : 2026-06-10T23:59:59 L'ingénierie de microbiomes est un domaine prometteur avec des applications dans de nombreux secteurs tels que l'environnement, l'agriculture, l'industrie agroalimentaire et la santé humaine. L'ingénierie de microbiomes consiste à concevoir et à manipuler des communautés microbiennes pour leur conférer une fonction souhaitée. Cette démarche s'appuie sur les propriétés écologiques de ces communautés, issues des interactions entre les micro-organismes, ainsi que leur structure, leur diversité fonctionnelle et leur stabilité. Dans ce projet de doctorat, des communautés microbiennes conçues par ingénierie de microbiomes seront étudiées pour leur capacité à produire des biomolécules antimicrobiennes innovantes. Des communautés disponibles au laboratoire seront décortiquées pour élucider les mécanismes écologiques et moléculaires à l'origine de leur activité antimicrobienne remarquable. Plus précisément, les interactions entre micro-organismes seront analysées afin de comprendre leur contribution au potentiel antimicrobien, tandis que des méthodes de caractérisation moléculaire seront employées pour identifier les molécules impliquées. Le projet mobilisera des approches de phénotypage à haut débit des interactions microbiennes, de microbiologie classique, de génomique et de spectrométrie de masse. The consumption of food contaminated with pathogens is an important cause of morbidity and mortality worldwide. Every year, approximately 600 million people - 1 in 10 people - get sick from foodborne pathogens, 420,000 of whom die. Human damage caused by foodborne pathogens results in colossal economic losses amounting to USD 110 billion due to lost productivity and health expenses (Borges et al., 2022a; World Health Organization, 2015).
Biopreservation refers to the use of beneficial microorganisms (such as lactic acid bacteria) producing antimicrobial substances to inhibit the growth of spoilage and pathogenic bacteria in food (Stiles, 1996). The primary antimicrobial agents used in biopreservation are bacteriocins, which are ribosomally synthesized antimicrobial peptides produced by bacteria to inhibit or kill closely related strains (Cotter et al., 2005). Bacteriocins such as nisin (from Lactococcus lactis) and pediocin (from Pediococcus acidilactici) are widely studied for their food preservation properties due to their safety and efficacy (Cleveland et al., 2001). The efficacy of biopreservation systems has been repeatedly demonstrated under laboratory conditions. However, their activity can be bacteriostatic (Cherrat et al., 2024; Engstrom et al., 2021; García et al., 2020; Muñoz et al., 2019; Wiernasz et al., 2020) or bactericidal (Goranov et al., 2022; Mathieu et al., 1994). Additionally, end-users of these technologies report variable effectiveness (personal communication). The variable efficacy of biopreservation systems, particularly those based on bacteriocins, is due to multiple interacting factors. Microbial strain specificity is a key limitation, as bacteriocins exhibit narrow-spectrum activity and may fail against resistant pathogens (Cotter et al., 2005). In addition, the activity of biopreservation systems depends on the physicochemical parameters such as pH, salt, and temperature, which are highly variable at spatial and temporal levels in food products, particularly in fermented food (Leroy and de Vuyst, 1999). Matrix rheological properties can influence the diffusion of antimicrobial compounds (Carnet Ripoche et al., 2006), and biochemical components such as lipids can also block the activity by interacting with bacteriocins (Chollet et al., 2008). More importantly, interactions with indigenous microbiota can either enhance or inhibit bacteriocin activity (Borges et al., 2022b). These various effects can be attributed to the very high variability in the composition of microbial communities colonizing foods. For example, for the same cheesemaking technology, the species present can vary considerably from one cheese to another (Irlinger et al., 2024). This paves the way for improved control over food functionality, particularly antimicrobial activity, by regulating the composition of food-colonizing microbiomes.
Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes (Albright et al., 2022). In microbiome engineering, top-down and bottom-up describe two opposite ways of controlling or constructing microbial communities. Bottom-up microbiome engineering assembles a subset of microorganisms with desired functions into a synthetic community (SynCom)(Henry and Bergelson, 2025). Lately, bottom-up microbiome engineering work conducted at LIBio has shown that it is possible to enhance anti-Listeria monocytogenes activity by assorting microorganisms with complementary antimicrobial effects (Mangavel et al., 2026). Top-down microbiome engineering starts from an existing, complex natural community and steering it toward a desired function by changing environmental or operating conditions such as pH, temperature, and nutrients. Top-down microbiome engineering has been successfully applied to screen microbial communities with improved function (Chang et al., 2021).
A critical point in top-down strategy is the stabilization of the structure of microbial communities before being scored for function. This stabilization can be obtained by serially passaging communities (Chang et al., 2021). By applying this very simple strategy, a set of 88 communities originating from raw milk were stabilized at the laboratory, characterized by metabarcoding, and then phenotyped at the LIBio (Thèse Léa-Jehanne Robert). Some microbial communities exhibited greater anti-L. monocytogenes activity than a patented strain of Carnobacterium maltaromaticum (LIBio), which is currently used in industrial applications (BORGES and REVOL-JUNELLES, 2024; Cherrat et al., 2024). However, the robustness of antimicrobial activity in relation to the variability of abiotic parameters is was not investigated during the course of Léa-Jehanne's PhD. Furthermore, the biomolecules and ecological mechanisms underlying such activities remain unknown.