Laurent Debarbieux

Website: https://research.pasteur.fr/fr/team/bacteriophage-bacterium-host
ORCID: 0000-0001-6875-5758
Twitter: @PhagePasteur

Our team is studying bacteriophages, the most abundant and diverse viruses specialized in the infection of bacteria. Our goal is to decipher the molecular mechanisms that bacteriophages deploy to infect bacteria within the mammalian host. We are using mainly two murine models to address two main questions.

First, we aim to identify the parameters governing the efficacy of the therapeutic use of bacteriophages (phage thereapy) to treat bacterial infections, and in particular pneumonia. We demonstrated that the efficacy of phage therapy rely on a synergistic action of bacteriophages with innate immune cells. With collaborators we are developing mathematical models to recapitulate the kinetics of phage therapy taking into account in vitro and in vivo data from tripartite interactions between bacteriophage, bacteria and the host.

Second, we study the role of bacteriophages in the intestinal microbiota and their impact on health. We are mainly using a gnotobiotic murine model (OMM12) to characterize the dynamics of prophage induction and their impact on microbiota stability and host responses. Currently we are evaluating the impact of several perturbations (pathogens, metabolites,…) on this controled intestinal microbial community.

We are please to share our expertise in bacteriophages and in particular their behaviour in complex ecosystems.

Top 5 publications

1. Delattre R, Seurat J, Haddad F, Nguyen TT, Gaborieau B, Kane R, Dufour N, Ricard JD, Guedj J, Debarbieux L. Combination of in vivo phage therapy data with in silico model highlights key parameters for pneumonia treatment efficacy. Cell Rep. 2022 May 17;39(7):110825. doi: 10.1016/j.celrep.2022.110825. PMID: 35584666
2. Lourenço M, Chaffringeon L, Lamy-Besnier Q, Titécat M, Pédron T, Sismeiro O, Legendre R, Varet H, Coppée JY, Bérard M, De Sordi L, Debarbieux L. The gut environment regulates bacterial gene expression which modulates susceptibility to bacteriophage infection. Cell Host Microbe. 2022 Apr 13;30(4):556-569.e5. doi: 10.1016/j.chom.2022.03.014. PMID: 35421351
3. Lamy-Besnier Q, Chaffringeon L, Lourenço M, Payne RB, Trinh JT, Schwartz JA, Sulakvelidze A, Debarbieux L. Prophylactic Administration of a Bacteriophage Cocktail Is Safe and Effective in Reducing Salmonella enterica Serovar Typhimurium Burden in Vivo. Microbiol Spectr. 2021 Sep 3;9(1):e0049721. doi: 10.1128/Spectrum.00497-21. Epub 2021 Aug 25. PMID: 34431719
4. Lourenço M, Chaffringeon L, Lamy-Besnier Q, Pédron T, Campagne P, Eberl C, Bérard M, Stecher B, Debarbieux L, De Sordi L. The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages. Cell Host Microbe. 2020 Sep 9;28(3):390-401.e5. doi: 10.1016/j.chom.2020.06.002. PMID: 32615090
5. Roach DR, Leung CY, Henry M, Morello E, Singh D, Di Santo JP, Weitz JS, Debarbieux L. Synergy between the Host Immune System and Bacteriophage Is Essential for Successful Phage Therapy against an Acute Respiratory Pathogen. Cell Host Microbe. 2017 Jul 12;22(1):38-47.e4. doi: 10.1016/j.chom.2017.06.018. PubMed PMID: 28704651.

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