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
Members
Publications
2024
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
2023
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
2023
Intrabacterial lipid inclusion‐associated proteins: a core machinery conserved from saprophyte Actinobacteria to the human pathogen Mycobacterium tuberculosis
Tonia Dargham, Ivy Mallick, Laurent Kremer, Pierre Santucci, Stéphane Canaan
FEBS Open Bio (2023)10.1002/2211-5463.13721
2023
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
2023
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
2023
Meet early career researcher—Ismath Sadhir—Awardee of the molecular microbiology poster prize at the EMBO workshop bacterial morphogenesis, survival and virulence: Dynamic genomes and envelopes
Pierre Santucci
Molecular Microbiology 120:103-104 (2023)10.1111/mmi.15111
2022
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
2022
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
2022
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
2022
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
2022
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
2021
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
2020
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
2020
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
2020
Experimental and computational investigation of Z/E isomerism, X-ray crystal structure and molecular docking study of (2-(hydroxyimino)cyclohexyl)diphenylphosphine sulfide, a potential antibacterial agent
Nejib Jebli, Youssef Arfaoui, Kristof van Hecke, Jean-François Cavalier, Soufiane Touil
Journal of Molecular Structure 129634 (2020)10.1016/j.molstruc.2020.129634
2020
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
2020
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
2019
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
2019
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
2019
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
2019
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
2019
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
2019
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
2019
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
2019
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
2018
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
2018
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
2018
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
2018
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
2018
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
2018
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
2018
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
2018
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
2017
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
2016
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
2015
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
2014
An interfacial and comparative in vitro study of gastrointestinal lipases and Yarrowia lipolytica LIP2 lipase, a candidate for enzyme replacement therapy
Anaïs Bénarouche, Vanessa Point, Frédéric Carrière, Jean-François Cavalier
Biochimie 102:145-153 (2014)10.1016/j.biochi.2014.03.004
2013
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
2013
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
2013
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
2013
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
2013
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
2012
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
2009
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
2005
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
2004
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
2003
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
2001
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
2000
2000
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
1999
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
1999
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
1999
New Synthesis of sn-1,2-and sn-2,3-O-Diacylglycerols ؊ Application to the Synthesis of Enantiopure Phosphonates Analogous to Triglycerides: A New Class of Inhibitors of Lipases
Frank Marguet, Jean-François Cavalier, Robert Verger, Gérard Buono
European Journal of Organic Chemistry (1999)
1998
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
Collaborations
- 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
Funding
