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

Publications

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 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 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

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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

2020
Classification and Nomenclature of Metacaspases and Paracaspases: No More Confusion with Caspases

Elena Minina, Jens Staal, Vanina Alvarez, John Berges, Ilana Berman-Frank, Rudi Beyaert, Kay Bidle, Frédéric Bornancin, Magali Casanova, Juan Cazzulo, Chang Jae Choi, Nuria Coll, Vishva Dixit, Marko Dolinar, Nicolas Fasel, Christiane Funk, Maurício F.M. Machado, Frank Madeo, Lynn Megeney, Panagiotis Moschou, Jeremy Mottram, Thomas Nyström, Heinz Osiewacz, Christopher Overall, Kailash Pandey, Jürgen Ruland, Guy Salvesen, Yigong Shi, Andrei Smertenko, Simon Stael, Jerry Ståhlberg, María Fernanda Suárez, Margot Thome, Hannele Tuominen, Frank van Breusegem, Renier A.L. van der Hoorn, Assaf Vardi, Boris Zhivotovsky, Eric Lam, Peter Bozhkov

Molecular Cell 77:927-929 (2020)10.1016/j.molcel.2019.12.020

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
Cell death in Leishmania

Louise Basmaciyan, Magali Casanova

Parasite 26:71 (2019)10.1051/parasite/2019071

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 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 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 Marsollier, Julie Géan, Erick Dufourc, Jean-François Cavalier, Stéphane Canaan, Agnès 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 & 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 Gnawali, Christopher Spilling, Jean-François Cavalier, Stéphane Canaan, Mickaël Blaise, Laurent Kremer

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

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

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

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

2000
Chlorosulfonyl Isocyanate

Jean-François Cavalier

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

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
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

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

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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

© 2021 LISM - Laboratoire d'Ingénierie des Systèmes Macromoléculaires - CNRS UMR7255

31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France