Our concern is to fight against pathogenic mycobacteria by studying lipid metabolism: identification / validation of proteins involved in lipid processes, discovery of new antimycobacterials (synthetic molecules, peptides) targeting lipid biosynthesis, and set up diagnostic tests related to lipid metabolism.

We aim at deciphering the physiological role of lipolytic enzymes involved in lipid metabolism in pathogenic mycobacteria (such as Mycobacterium tuberculosis, M. abscessus, M. marinum, M. ulcerans), their regulation during the infection process and their impact in dormancy phase. As lipid metabolism is directly related to the viability and virulence of mycobacteria, we also develop specific models to study these enzymes and their inhibitors in order to regulate this metabolic pathway and therefore the spread of the disease.

We have established that these enzymes are involved in bacterial growth, virulence (reactivation and propagation), dormancy, lipid storage and degradation as well as in cell wall biosynthesis.

Moreover, our work leads to the discovery of two new families of lipolytic enzyme inhibitors with strong anti-tuberculous effects, which are useful probes to study mycobacterial lipid metabolism, thus opening a new way to fight the disease.

The team’s expertise range from protein biochemistry (purification, biochemical characterization, expression of recombinant protein using E. coli, M. smegmatis, P. Pastoris or baculovirus expression systems), molecular and cell biology (construction of mutant strains, cell infection), lipid analysis to medicinal chemistry (organic synthesis, in silico docking, enzymology, susceptibility testing…) and cell imaging (fluorescence and electron microscopy).

For more details, please visit us at LBPTeam


Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus

Magali Casanova, Marc Maresca, Isabelle Poncin, Vanessa Point, Hamza Olleik, Céline Boidin-Wichlacz, Aurélie Tasiemski, Kamel Mabrouk, Jean-François Cavalier, Stéphane Canaan

Journal of Biomedical Science 31:18 (2024)10.1186/s12929-024-01007-8

Evaluation of the Efficiency of Random and Diblock Methacrylate-Based Amphiphilic Cationic Polymers against Major Bacterial Pathogens Associated with Cystic Fibrosis

Magali Casanova, Hamza Olleik, Slim Hdiouech, Clarisse Roblin, Jean-François Cavalier, Vanessa Point, Katy Jeannot, Baptiste Caron, Josette Perrier, Siméon Charriau, Mickael Lafond, Yohann Guillaneuf, Stéphane Canaan, Catherine Lefay, Marc Maresca

Antibiotics 12:120 (2023)10.3390/antibiotics12010120

Activity and Crystal Structure of the Adherent-Invasive Escherichia coli Tle3/Tli3 T6SS Effector/Immunity Complex Determined Using an AlphaFold2 Predicted Model

Thi Thu Hang Le, Christine Kellenberger, Marie Boyer, Pierre Santucci, Nicolas Flaugnatti, Eric Cascales, Alain Roussel, Stéphane Canaan, Laure Journet, Christian Cambillau

International Journal of Molecular Sciences 24:1740 (2023)10.3390/ijms24021740

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Peroxisomal ROS control cytosolic Mycobacterium tuberculosis replication in human macrophages

Enrica Pellegrino, Beren Aylan, Claudio Bussi, Antony Fearns, Elliott Bernard, Natalia Athanasiadi, Pierre Santucci, Laure Botella, Maximiliano Gutierrez

Journal of Cell Biology 222:e202303066 (2023)10.1083/jcb.202303066

Direct capture, inhibition and crystal structure of HsaD (Rv3569c) from M. tuberculosis

Sarah Barelier, Romain Avellan, Giri Raj Gnawali, Patrick Fourquet, Véronique Roig-Zamboni, Isabelle Poncin, Vanessa Point, Yves Bourne, Stéphane Audebert, Luc Camoin, Christopher Spilling, Stéphane Canaan, Jean‐françois Cavalier, Gerlind Sulzenbacher

FEBS Journal (2022)10.1111/febs.16645

Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism

Claudio Bussi, Tiaan Heunis, Enrica Pellegrino, Elliott Bernard, Nourdine Bah, Mariana Silva dos Santos, Pierre Santucci, Beren Aylan, Angela Rodgers, Antony Fearns, Julia Mitschke, Christopher Moore, James Macrae, Maria Greco, Thomas Reinheckel, Matthias Trost, Maximiliano Gutierrez

Nature Communications 13:7338 (2022)10.1038/s41467-022-34632-8

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2

Laura Caccialupi da Prato, Ugo Zayan, Dina Abdallah, Vanessa Point, Fabienne Schaller, Emilie Pallesi-Pocachard, Aurélie Montheil, Stéphane Canaan, Jean-Luc Gaiarsa, Françoise Muscatelli, Valéry Matarazzo

Neuropsychopharmacology (2022)10.1038/s41386-022-01313-5

Design, synthesis and antibacterial activity against pathogenic mycobacteria of conjugated hydroxamic acids, hydrazides and O-alkyl/O-acyl protected hydroxamic derivatives

Vasiliki Mavrikaki, Alexandros Pagonis, Isabelle Poncin, Ivy Mallick, Stéphane Canaan, Victoria Magrioti, Jean-François Cavalier

Bioorganic and Medicinal Chemistry Letters 64:128692 (2022)10.1016/j.bmcl.2022.128692

Synthesis and Biological Characterization of Fluorescent Cyclipostins and Cyclophostin Analogues: New Insights for the Diagnosis of Mycobacterial-Related Diseases

Morgane Sarrazin, Benjamin Martin, Romain Avellan, Giri Raj Gnawali, Isabelle Poncin, Hugo Le Guenno, Christopher Spilling, Jean-François Cavalier, Stéphane Canaan

ACS Infectious Diseases (2022)10.1021/acsinfecdis.2c00448

Intrabacterial lipid inclusions in mycobacteria: unexpected key players in survival and pathogenesis?

Ivy Mallick, Pierre Santucci, Isabelle Poncin, Vanessa Point, Laurent Kremer, Jean-François Cavalier, Stéphane Canaan

FEMS Microbiology Reviews (2021)10.1093/femsre/fuab029

Lipolytic enzymes inhibitors: A new way for antibacterial drugs discovery

Jean-François Cavalier, Christopher D Spilling, Thierry Durand, Luc Camoin, Stéphane Canaan

European Journal of Medicinal Chemistry 112908 (2020)10.1016/j.ejmech.2020.112908

Structural basis for loading and inhibition of a bacterial T6 SS phospholipase effector by the VgrG spike

Nicolas Flaugnatti, Chiara Rapisarda, Martial Rey, Solène G Beauvois, Viet Anh Nguyen, Stéphane Canaan, Eric Durand, Julia Chamot‐rooke, E. Cascales, Rémi Fronzes, Laure Journet

EMBO Journal 39:e104129 (2020)10.15252/embj.2019104129

Synthesis, antimicrobial activity and molecular docking study of novel α‐(diphenylphosphoryl)‐ and α‐(diphenylphosphorothioyl)cycloalkanone oximes

Nejib Jebli, Selma Hamimed, Kristof van Hecke, Jean-François Cavalier, Soufiane Touil

Chemistry and Biodiversity 17:e2000217 (2020)10.1002/cbdv.202000217

Dissecting the antibacterial activity of oxadiazolone-core derivatives against Mycobacterium abscessus

Abdeldjalil Madani, Ivy Mallick, Alexandre Guy, Céline Crauste, Thierry Durand, Patrick Fourquet, Stéphane Audebert, Luc Camoin, Stéphane Canaan, Jean-François Cavalier

PLoS ONE 15:e0238178 (2020)10.1371/journal.pone.0238178

Haloarcula sebkhae sp. nov., an extremely halophilic archaeon from Algerian hypersaline environment

Hélène Barreteau, Manon Vandervennet, Laura Guedon, Vanessa Point, Stéphane Canaan, Sylvie Rebuffat, Jean Peduzzi, Alyssa Carré-Mlouka

International Journal of Systematic and Evolutionary Microbiology 69 (2019)10.1099/ijsem.0.003211

Design, synthesis, antimicrobial evaluation, and molecular docking studies of novel symmetrical 2,5‐difunctionalized 1,3,4‐oxadiazoles

Shaima Hkiri, Afifa Hafidh, Jean-François Cavalier, Soufiane Touil, Ali Samarat

Journal of Heterocyclic Chemistry (2019)10.1002/jhet.3837

Cyclipostins and Cyclophostin Analogues as Multitarget Inhibitors That Impair Growth of Mycobacterium abscessus

Abdeldjalil Madani, Jeremy Ridenour, Benjamin Martin, Rishi Paudel, Anosha Abdul Basir, Vincent Le Moigne, Jean-Louis Herrmann, Stéphane Audebert, Luc Camoin, Laurent Kremer, Christopher D Spilling, Stéphane Canaan, Jean-François Cavalier

ACS Infectious Diseases (2019)10.1021/acsinfecdis.9b00172

Worms’ Antimicrobial Peptides

Bruno Renato, Marc Maresca, Stéphane Canaan, Jean-François Cavalier, Kamel Mabrouk, Céline Boidin-Wichlacz, Hamza Olleik, Daniela Zeppilli, Priscille Brodin, François Massol, Didier Jollivet, Sacha Jung, Aurélie Tasiemski

Marine drugs 17:512 (2019)10.3390/md17090512

Dissecting the membrane lipid binding properties and lipase activity of Mycobacterium tuberculosis LipY domains

Pierre Santucci, Nabil Smichi, Sadia Diomandé, Isabelle Poncin, Vanessa Point, Hélène Gaussier, Jean-François Cavalier, Laurent Kremer, Stéphane Canaan

FEBS Journal (2019)10.1111/febs.14864

Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria

Pierre Santucci, Matt Johansen, Vanessa Point, Isabelle Poncin, Albertus Viljoen, Jean-François Cavalier, Laurent Kremer, Stéphane Canaan

Scientific Reports 9 (2019)10.1038/s41598-019-45164-5

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

Pierre Santucci, Christina Dedaki, Alexandros Athanasoulis, Laura Gallorini, Anaïs Munoz, Stéphane Canaan, Jean-François Cavalier, Victoria Magrioti

ChemMedChem 14:349-358 (2019)10.1002/cmdc.201800720

Methyl arachidonyl fluorophosphonate inhibits Mycobacterium tuberculosis thioesterase TesA and globally affects vancomycin susceptibility

Dong Yang, Guy Vandenbussche, Didier Vertommen, Damien Evrard, Romany Abskharon, Jean-François Cavalier, Gilles Berger, Stéphane Canaan, Mohammad Shahneawz Khan, Sheng Zeng, Alexandre Wohlkonig, Martine Prévost, Patrice Soumillion, Véronique Fontaine

FEBS Letters (2019)10.1002/1873-3468.13555

Biochemical and Structural Characterization of TesA, a Major Thioesterase Required for Outer-Envelope Lipid Biosynthesis in Mycobacterium tuberculosis

Phuong Chi Nguyen, van Son Nguyen, Benjamin Martin, Patrick Fourquet, Luc Camoin, Chistopher Spilling, Jean-François Cavalier, Christian Cambillau, Stéphane Canaan

Journal of Molecular Biology 430:5129-5136 (2018)10.1016/j.jmb.2018.09.017

Oxadiazolone derivatives, new promising multi-target inhibitors against M. tuberculosis

Phuong Chi Nguyen, Vincent Delorme, Anaïs Benarouche, Alexandre Guy, Valérie Landry, Stéphane Audebert, Matthieu Pophillat, Luc Camoin, Céline Crauste, Jean-Marie Galano, Thierry Durand, Priscille Brodin, Stéphane Canaan, Jean-François Cavalier

Bioorganic Chemistry 81:414-424 (2018)10.1016/j.bioorg.2018.08.025

Cyclophostin and Cyclipostins analogues, new promising molecules to treat mycobacterial-related diseases

Phuong Nguyen, Abdeldjalil Madani, Pierre Santucci, Benjamin Martin, Rishi R Paudel, Sandrine Delattre, Jean-Louis Herrmann, Christopher D Spilling, Laurent Kremer, Jean-François Cavalier, Stéphane Canaan

International Journal of Antimicrobial Agents (2018)10.1016/j.ijantimicag.2017.12.001

The potent effect of mycolactone on lipid membranes

Milène Nitenberg, Anaïs Benarouche, Ofélia Maniti, Estelle Marion, Laurent L Marsollier, Julie Géan, Erick J Dufourc, Jean-François Cavalier, Stéphane Canaan, Agnès P Girard-Egrot

PLoS Pathogens 14:e1006814 (e-collection 2018 jan) (2018)10.1371/journal.ppat.1006814

Delineating the Physiological Roles of the PE and Catalytic Domains of LipY in Lipid Consumption in Mycobacterium-Infected Foamy Macrophages

Pierre Santucci, Sadia Diomandé, Isabelle Poncin, Laetitia Alibaud, Albertus Viljoen, Laurent Kremer, Chantal de Chastellier, Stéphane Canaan

Infection and Immunity 86 (2018)10.1128/IAI.00394-18

LipG a bifunctional phospholipase/thioesterase involved in mycobacterial envelope remodeling

Pierre Santucci, Vanessa Point, Isabelle Poncin, Alexandre Guy, Céline Crauste, Carole Serveau-Avesque, Jean marie Galano, Chistopher d. Spilling, Jean-François Cavalier, Stéphane Canaan

Bioscience Reports 38:BSR20181953 (2018)10.1042/BSR20181953

Lipid Droplets Breakdown: Adipose Triglyceride Lipase Leads the Way

Pierre Santucci, Stéphane Canaan

Current Protein and Peptide Science 19:1131-1133 (2018)10.2174/1389203719666180809143000

Cyclipostins and cyclophostin analogs inhibit the antigen 85C from Mycobacterium tuberculosis both in vitro and in vivo

Albertus Viljoen, Matthias Richard, Phuong Chi Nguyen, Patrick Fourquet, Luc Camoin, Rishi R. Paudal, Giri R Gnawali, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan, Mickaël Blaise, Laurent Kremer

Journal of Biological Chemistry 293:2755-2769 (2018)10.1074/jbc.RA117.000760

Efficient synthesis of novel dialkyl-3-cyanopropylphosphate derivatives and evaluation of their anticholinesterase activity

Iyadh Aouani, Badreddine Sellami, Karima Lahbib, Jean-François Cavalier, Soufiane Touil

Bioorganic Chemistry 72:301-307 (2017)10.1016/j.bioorg.2017.05.008

A phospholipase A 1 antibacterial Type VI secretion effector interacts directly with the C-terminal domain of the VgrG spike protein for delivery

Nicolas Flaugnatti, Thi Thu Hang Le, Stéphane Canaan, Marie-Stéphanie Aschtgen, Vân Nguyên, Stephanie Blangy, Christine Kellenberger, Alain Roussel, Christian Cambillau, E. Cascales, Laure Journet

Molecular Microbiology 99:1099-1118 (2016)10.1111/mmi.13292

Biochemical characterization of Yarrowia lipolytica LIP8, a secreted lipase with a cleavable C-terminal region

Jannet Kamoun, Mathieu Schué, Wala Messaoud, Justine Baignol, Vanessa Point, Eduardo Mateos-Diaz, Pascal Mansuelle, Youssef Gargouri, Goetz Parsiegla, Jean-François Cavalier, Frédéric Carrière, Ahmed Aloulou

Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids 1851:129-140 (2015)10.1016/j.bbalip.2014.10.012

Solution conformational features and interfacial properties of an intrinsically disordered peptide coupled to alkyl chains: a new class of peptide amphiphiles

Antonella Accardo, Marilisa Leone, Diego Tesauro, Rosa Aufiero, Anaïs Bénarouche, Jean-François Cavalier, Sonia Longhi, Frederic Carriere, Filomena Rossi

Molecular BioSystems 9:1401 (2013)10.1039/c3mb25507g

Biochemical and structural characterization of non-glycosylated Yarrowia lipolytica LIP2 lipase

Ahmed Aloulou, Anaïs Bénarouche, Delphine Puccinelli, Silvia Spinelli, Jean-François Cavalier, Christian Cambillau, Frédéric Carrière

European Journal of Lipid Science and Technology 115:429-441 (2013)10.1002/ejlt.201200440

New insights into the pH-dependent interfacial adsorption of dog gastric lipase using the monolayer technique

Anaïs Bénarouche, Vanessa Point, Goetz Parsiegla, Frédéric Carrière, Jean-François Cavalier

Colloids and Surfaces B: Biointerfaces 111:306-312 (2013)10.1016/j.colsurfb.2013.06.025

Effects of the propeptide of group X secreted phospholipase A2 on substrate specificity and interfacial activity on phospholipid monolayers

Vanessa Point, Anaïs Bénarouche, Ikram Jemel, Goetz Parsiegla, Gérard Lambeau, Frédéric Carrière, Jean-François Cavalier

Biochimie 95:51-58 (2013)10.1016/j.biochi.2012.07.023

Enantioselective Inhibition of Microbial Lipolytic Enzymes by Nonracemic Monocyclic Enolphosphonate Analogues of Cyclophostin

Vanessa Point, Raj Malla, Frederic Carrière, Stéphane Canaan, Christopher Spilling, Jean-François Cavalier

Journal of Medicinal Chemistry 56:4393-4401 (2013)10.1021/jm4000787

Synthesis and Kinetic Evaluation of Cyclophostin and Cyclipostins Phosphonate Analogs As Selective and Potent Inhibitors of Microbial Lipases

Vanessa Point, Raj Malla, Sadia Diomande, Benjamin Martin, Vincent Delorme, Frederic Carriere, Stephane Canaan, Nigam Rath, Christopher Spilling, Jean-François Cavalier

Journal of Medicinal Chemistry 55:10204-10219 (2012)10.1021/jm301216x

Synthesis, Structure-activity Relationship and In Vitro Evaluation of Coelenterazine and Coelenteramine Derivatives as Inhibitors of Lipid Peroxidation

Maggi Burton, Catherine de Tollenaere, Jean-François Cavalier, Cécile Marchand, Frédérique Dussart, Jacqueline Marchand-Brynaert, Jean-François Rees

Free Radical Research 37:145-158 (2009)10.1080/1071576021000036443

Discrimination between closed and open forms of lipases using electrophoretic techniques

Jean-François Cavalier, N. Miled, M. Riviere, J.F. Cavalier, G. Buono, L. Berti, R. Verger

Analytical Biochemistry 338:171-178 (2005)10.1016/j.ab.2004.11.046

2,6-Diamino-3,5-diaryl-1,4-pyrazine Derivatives as Novel Antioxidants

Jean-François Cavalier, Maggi Burton, Catherine de Tollenaere, Frédérique Dussart, Cécile Marchand, Jean-François Rees, Jacqueline Marchand-Brynaert

Synthesis: Journal of Synthetic Organic Chemistry 2001:0768-0772 (2004)10.1055/s-2001-12764

N -(Alkyl)-2-amino-1,4-pyrazine Derivatives: Synthesis and Antioxidative Properties of 3- and 3,5- p -Hydroxyphenyl-Substituted Compounds

Paul Jeanjot, Frédéric Bruyneel, Axelle Arrault, Sonia Gharbi, Jean-François Cavalier, Agnès Abels, Cécile Marchand, Roland Touillaux, Jean-François Rees, Jacqueline Marchand-Brynaert

Synthesis: Journal of Synthetic Organic Chemistry 2003:0513-0522 (2003)10.1055/s-2003-37652

Catechol derivatives of aminopyrazine and cell protection against uvb-induced mortality

Jean-François Cavalier, Maggi Burton, Frédérique Dussart, Cécile Marchand, Jean-François Rees, Jacqueline Marchand-Brynaert

Bioorganic and Medicinal Chemistry Letters 9:1037-1044 (2001)10.1016/s0968-0896(00)00321-7

Chlorosulfonyl Isocyanate

Jean-François Cavalier

SYNLETT 2000:427 (2000)10.1055/s-2000-6546

Covalent Inhibition of Digestive Lipases by Chiral Phosphonates

Jean-François Cavalier, Gerard Buono, Robert Verger

Accounts of Chemical Research 33:579-589 (2000)10.1021/ar990150i

Inhibition of human gastric and pancreatic lipases by chiral alkylphosphonates. A kinetic study with 1,2-didecanoyl-sn-glycerol monolayer

Jean-François Cavalier, Stéphane Ransac, Robert Verger, Gérard Buono

Chemistry and Physics of Lipids 100:3-31 (1999)10.1016/s0009-3084(99)00028-6

Interfacial and/or molecular recognition by lipases of mixed monomolecular films of 1,2-dicaprin and chiral organophosphorus glyceride analogues?

Frank Marguet, Isabelle Douchet, Jean-François Cavalier, Gerard Buono, Robert Verger

Colloids and Surfaces B: Biointerfaces 13:37-45 (1999)10.1016/S0927-7765(98)00099-X

New Highly Diastereoselective Synthesis of Phosphoramidates. A Route to Chiral Methyl p -Nitrophenyl Alkylphosphonates

Jean-François Cavalier, Frédéric Fotiadu, Robert Verger, Gérard Buono

SYNLETT 1998:73-75 (1998)10.1055/s-1998-1560

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  • National
    • J.-L. Hermann APHP Paris
    • L. Kremer Irim Montpellier
    • L. Marsollier Inserm Angers
  • International
    • V. Magrioti University of Athens, Greece
    • C. D. Spilling University of Missouri, St Louis, USA


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