Mycobacterial Pathogenesis and Novel Therapeutic Targets

THE PROJECTS

Mycobacterium tuberculosis, the etiologic agent of tuberculosis, represents a major cause of death worldwide due to a unique infectious agent. Since the mid-80s, there has been a prominent progression of the disease, substantiated by the spread of the HIV pandemic and the emergence of multidrug-resistant M. tuberculosis strains. In addition, atypical mycobacteria, including Mycobacterium abscessus, represent an emerging health problem in industrialized countries, and are notorious for being highly resistant to most antibiotic treatments. Thus, there is an urgent need to develop new therapies to combat these infections. One key aspect characterizing pathogenic mycobacteria resides in their capacity to persist within the phagocytic cells for several years/decades, which is strongly associated with the presence of a very unusual cell envelope. These cell wall components play a key role in driving host-pathogen interactions necessary for the establishment and persistence of the infection and represent valid targets for several antitubercular drugs.

In this context, we explore the mycobacterial cell envelope to decipher its role in the physiopathological events characterizing the infection and to identify new pharmacological targets. Our work focuses on major cell wall (glycol)lipidic components with respect to their biosynthesis, regulation, and contribution/role in virulence in pathogenic mycobacteria. 

Our research program aims to investigate virulence factors in Mycobacterium tuberculosis as well as in non-tuberculous mycobacteria, such as M. abscessus, by studying genes involved in biosynthesis, catabolism and transport of mycobacterial cell wall components. Among these components are mycolic acids (long-chain fatty acids) and a vast array of lipids and glycolipids sharing exotic structures and participating in the immunopathology of the infection. Besides determining the metabolic pathways and the mechanisms controlling expression of these molecules, we are also interested in elucidating the structures of the (glycol)lipid components and their biological functions to better define their role in the physiopathology of the infection and to discover new targets of pharmacological interest. The molecular mechanisms responsible for virulence and physiopathology of atypical mycobacteria remaining elusive, we also develop alternative models of infection to apprehend and describe new mechanisms of immune evasion and persistence in the infected host.

Our studies can be summarized by 3 mains interconnected goals.

  • Aim 1: Microbiology of tuberculous and non-tuberculous mycobacteria.

We focus essentially on the biosynthetic and catabolic pathways of lipidic and glycolipidic cell wall associated components.

Genetic, biochemical and crystallographic studies are employed to discover and characterize enzymes involved in the biosynthesis, transport and remodeling of the mycobacterial cell wall. The objective here consists of understanding the role of components of the envelope in the adaptation of pathogenic mycobacteria to their environment and to establish a successful infection process within the host as well as to identify and validate new targets of therapeutic interest to fight against mycobacterial infections. This aim includes also the elucidation of structures and biological functions of glycolipids in atypical mycobacteria (M. marinum and M. abscessus complex) and to determine their contribution in the the pro-inflammatory response and granuloma formation.


Schematic structure of the mycobacterial envelope. Besides a plasmic membrane, the cell wall consists of a complex network of proteins, lipoglycans and (glyco)lipids, which participate directly in the interaction with the host cells. Because of their uniqueness in Mycobacterium, the enzymes involved in the biosynthesis of the cell wall components represent attractive targets for future drug development.

  • Aim 2: Mode of action of antimycobacterial drugs.

We study the mechanisms of activation and action of molecules inhibiting the biosynthesis of cell wall components, with a special emphasis on mycolic acids.

This aim consists essentially of determining the molecular targets and mode of action of several antimycobacterial drugs, of synthesizing structural analogues that are more efficient and less toxic than the parental molecules and to evaluate the anti-mycobacterial properties of these compounds in vitro and in vivo in a zebrafish model of infection (see Aim 3).

Another key aspect of this axis consists to describe the mechanisms responsible for the intrinsic resistance of atypical mycobacteria to most antitubercular drugs and to discover new active molecules against these species. This implies the screening of chemical libraries, the selection of resistant strains to the selected active inhibitors and identification/characterization of the therapeutic targets through the combination of genetic/biochemical and crystallographic techniques.


 
Three-dimensional structure of Ag85C bound to a potent inhibitor cyclophostin

  • Aim 3: Alternative models of infection to study mycobacterial virulence.

     We develop amoeba and zebrafish (Danio rerio) models to identify new virulence genes and to image in real time the chronology of the infection.

The amoeba model is particularly adapted to the screening of transposon libraries to select for instance attenuated mutants of M. marinum or M. abscessus and to evaluate and compare their capacity of intracellular growth and survival. The zebrafish is also used to evaluate and compare virulence of mutants and, due to its optical transparency, this model is particularly suited to image the infection process at a spatiotemporal level. In this context, it has been successfully used to propose mycobacterial cords as a new mechanism of immune evasion by preventing mycobacteria to be phagocytosed by macrophages and neutrophils. In addition, embryos can be used to visualize, in real time, the pharmacological activity of molecules/drugs or to study the role of cell wall components in the induction of an inflammatory granulomatous response during infection with M. marinum and M. abscessus.

Zebrafish embryo infected with the rough variant of M. abscessus expressing mCherry (red). Microinjection was performed in the caudal vein in the mpx::GFP transgenic line harbouring green fluorescent neutrophils. The image shows the presence of a massive mycobacterial cord (red) surrounded by neuthrophils (green) in the brain.


POST-DOC, PhD and undergraduate students

We are looking for strong candidates (microbiologists, biochemists, structural biologists) as well as researchers or technicians/engineers with positions at CNRS, INSERM or University who are interested by our interdisciplinary approaches, combining basic and translational research in mycobacteriology.




 

2018

Delineating the physiological roles of the PE and catalytic domain of LipY in lipid consumption in mycobacteria-infected foamy macrophages.

Santucci P, Diomandé S, Poncin I, Alibaud L, Viljoen A, Kremer L, de Chastellier C, Canaan S. Infect Immun. 2018 Jul 9. pii: IAI.00394-18. doi: 10.1128/IAI.00394-18.

Glycopeptidolipids, a Double-Edged Sword of the Mycobacterium abscessus Complex.

Gutiérrez AV, Viljoen A, Ghigo E, Herrmann JL, Kremer L.
Front Microbiol. 2018 Jun 5;9:1145. doi: 10.3389/fmicb.2018.01145. eCollection 2018. Review.

Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis β-ketoacyl-acyl carrier protein reductase MabA.

Küssau T, Flipo M, Van Wyk N, Viljoen A, Olieric V, Kremer L, Blaise M.
Acta Crystallogr D Struct Biol. 2018 May 1;74(Pt 5):383-393. doi:10.1107/S2059798318002917.

B cells response directed against Cut4 and CFP21 lipolytic enzymes in active and latent tuberculosis infections.

Rénier W, Bourdin A, Rubbo PA, Peries M, Dedieu L, Bendriss S, Kremer L, Canaan S, Terru D, Godreuil S, Nagot N, Van de Perre P, Tuaillon E.
PLoS One. 2018 Apr 30;13(4):e0196470. doi: 10.1371/journal.pone.0196470.

Mechanistic and Structural Insights Into the Unique TetR-Dependent Regulation of a Drug Efflux Pump in Mycobacterium abscessus.

Richard M, Gutiérrez AV, Viljoen AJ, Ghigo E, Blaise M, Kremer L.
Front Microbiol. 2018 Apr 5;9:649. doi: 10.3389/fmicb.2018.00649.

Neutrophil killing of Mycobacterium abscessus by intra- and extracellular mechanisms.

Malcolm KC, Caceres SM, Pohl K, Poch KR, Bernut A, Kremer L, Bratton DL, Herrmann JL, Nick JA.
PLoS One. 2018 Apr 19;13(4):e0196120. doi: 10.1371/journal.pone.0196120.

Alkylated/aminated nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates: Synthesis and anti-mycobacterial evaluation.

Shalini, Viljoen A, Kremer L, Kumar V.
Bioorg Med Chem Lett. 2018 Mar 8. pii: S0960-894X(18)30200-2. doi:10.1016/j.bmcl.2018.03.021.

A Simple and Rapid Gene Disruption Strategy in Mycobacterium abscessus: On the Design and Application of Glycopeptidolipid Mutants.

Viljoen A, Gutiérrez AV, Dupont C, Ghigo E, Kremer L.
Front Cell Infect Microbiol. 2018 Mar 14;8:69. doi: 10.3389/fcimb.2018.00069.

Identification of genes required for Mycobacterium abscessus growth in vivo with a prominent role of the ESX-4 locus.

Laencina L, Dubois V, Le Moigne V, Viljoen A, Majlessi L, Pritchard J, Bernut A, Piel L, Roux AL, Gaillard JL, Lombard B, Loew D, Rubin EJ, Brosch R, Kremer L, Herrmann JL, Girard-Misguich F.
Proc Natl Acad Sci U S A. 2018 Jan 17. pii: 201713195. doi:10.1073/pnas.1713195115.

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

Viljoen A, Richard M, Nguyen PC, Fourquet P, Camoin L, Paudal RR, Gnawali GR, Spilling CD, Cavalier JF, Canaan S, Blaise M, Kremer L.
J Biol Chem. 2018 Feb 23;293(8):2755-2769. doi: 10.1074/jbc.RA117.000760. Epub 2018 Jan 4.

2017

Cyclophostin and cyclipostins analogs, new promising molecules to treat mycobacterial-related diseases.

Nguyen PC, Madani A, Santucci P, Martin BP, Paudel RR, Delattre S, Herrmann JL, Spilling CD, Kremer L, Canaan S, Cavalier JF.
Int J Antimicrob Agents. 2017 Dec 11. pii: S0924-8579(17)30435-1. doi: 10.1016/j.ijantimicag.2017.12.001. 

Severe inhibition of lipooligosaccharide synthesis induces TLR2-dependent elimination of Mycobacterium marinum from THP1-derived macrophages.

Szulc-Kielbik I, Pawelczyk J, Kielbik M, Kremer L, Dziadek J, Klink M.
Microb Cell Fact. 2017 Nov 28;16(1):217. doi: 10.1186/s12934-017-0829-z.

Cyclipostins and Cyclophostin analogs as promising compounds in the fight against tuberculosis.

Nguyen PC, Delorme V, Bénarouche A, Martin BP, Paudel R, Gnawali GR, Madani A, Puppo R, Landry V, Kremer L, Brodin P, Spilling CD, Cavalier JF, Canaan S.
Sci Rep. 2017 Sep 18;7(1):11751. doi: 10.1038/s41598-017-11843-4.

Controlling Extra- and Intramacrophagic Mycobacterium abscessus by Targeting Mycolic Acid Transport.

Viljoen A, Herrmann JL, Onajole OK, Stec J, Kozikowski AP, Kremer L.
Front Cell Infect Microbiol. 2017 Sep 1;7:388. doi: 10.3389/fcimb.2017.00388. eCollection 2017.

Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry.

Fu J, Fu H, Dieu M, Halloum I, Kremer L, Xia Y, Pan W, Vincent SP.
Chem Commun (Camb). 2017 Sep 14. doi: 10.1039/c7cc05251k.

Azide-alkyne cycloaddition en route to 4-aminoquinoline-ferrocenylchalcone conjugates: synthesis and anti-TB evaluation.

Singh A, Viljoen A, Kremer L, Kumar V.
Future Med Chem. 2017 Sep 4. doi: 10.4155/fmc-2017-0098.

Bedaquiline inhibits the ATP synthase in Mycobacterium abscessus and is effective in infected zebrafish.

Dupont C, Viljoen A, Thomas S, Roquet-Banères F, Herrmann JL, Pethe K, Kremer L.
Antimicrob Agents Chemother. 2017 Aug 14. pii: AAC.01225-17. doi: 10.1128/AAC.01225-17.

Targeting Mycolic Acid Transport by Indole-2-carboxamides for the Treatment of Mycobacterium abscessus Infections.

Kozikowski AP, Onajole OK, Stec J, Dupont C, Viljoen A, Richard M, Chaira T, Lun S, Bishai W, Raj VS, Ordway D, Kremer L.
J Med Chem. 2017 Jul 13;60(13):5876-5888. doi: 10.1021/acs.jmedchem.7b00582.

Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM Inhibitors.

Villaume SA, Fu J, N'Go I, Liang H, Lou H, Kremer L, Pan W, Vincent SP.
Chemistry. 2017 Aug 1;23(43):10423-10429. doi: 10.1002/chem.201701812.

The Diverse Cellular and Animal Models to Decipher the Physiopathological Traits of Mycobacterium abscessus Infection.

Bernut A, Herrmann JL, Ordway D, Kremer L.
Front Cell Infect Microbiol. 2017 Apr 4;7:100. doi: 10.3389/fcimb.2017.00100. eCollection 2017. Review.

The diverse family of MmpL transporters in mycobacteria: from regulation to antimicrobial developments.

Viljoen A, Dubois V, Girard-Misguich F, Blaise M, Herrmann JL, Kremer L.
Mol Microbiol. 2017 Jun;104(6):889-904. doi: 10.1111/mmi.13675. Epub 2017 Apr 18. Review.

Acid-Fast Positive and Acid-Fast Negative Mycobacterium tuberculosis: The Koch Paradox.

Vilchèze C, Kremer L.
Microbiol Spectr. 2017 Mar;5(2). doi: 10.1128/microbiolspec.TBTB2-0003-2015. Review.

The influence of AccD5 on AccD6 carboxyltransferase essentiality in pathogenic and non-pathogenic Mycobacterium.

Pawelczyk J, Viljoen A, Kremer L, Dziadek J.
Sci Rep. 2017 Feb 16;7:42692. doi: 10.1038/srep42692.

Characterization of a mycobacterial cellulase and its impact on biofilm- and drug-induced cellulose production.

Van Wyk N, Navarro D, Blaise M, Berrin JG, Henrissat B, Drancourt M, Kremer L.
Glycobiology. 2017 May 1;27(5):392-399. doi: 10.1093/glycob/cwx014.

Binding of NADP+ triggers an open-to-closed transition in a mycobacterial FabG β-ketoacyl-ACP reductase.

Blaise M, Van Wyk N, Banères-Roquet F, Guérardel Y, Kremer L.
Biochem J. 2017 Mar 7;474(6):907-921. doi: 10.1042/BCJ20161052.

Resistance to Thiacetazone Derivatives Active against Mycobacterium abscessus Involves Mutations in the MmpL5 Transcriptional Repressor MAB_4384.

Halloum I, Viljoen A, Khanna V, Craig D, Bouchier C, Brosch R, Coxon G, Kremer L.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02509-16. doi: 10.1128/AAC.02509-16.

Inhibition of the β-Lactamase BlaMab by Avibactam Improves the In Vitro and In Vivo Efficacy of Imipenem against Mycobacterium abscessus.

Lefebvre AL, Le Moigne V, Bernut A, Veckerlé C, Compain F, Herrmann JL, Kremer L, Arthur M, Mainardi JL.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02440-16. doi: 10.1128/AAC.02440-16.

Current perspectives on the families of glycoside hydrolases of Mycobacterium tuberculosis: their importance and prospects for assigning function to unknowns.

van Wyk N, Drancourt M, Henrissat B, Kremer L.
Glycobiology. 2017 Jan;27(2):112-122. doi: 10.1093/glycob/cww099.

Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea.

Velappan AB, Charan Raja MR, Datta D, Tsai YT, Halloum I, Wan B, Kremer L, Gramajo H, Franzblau SG, Kar Mahapatra S, Debnath J.
Eur J Med Chem. 2017 Jan 5;125:825-841. doi: 10.1016/j.ejmech.2016.09.083.

2016

The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages.

Roux AL, Viljoen A, Bah A, Simeone R, Bernut A, Laencina L, Deramaudt T, Rottman M, Gaillard JL, Majlessi L, Brosch R, Girard-Misguich F, Vergne I, de Chastellier C, Kremer L, Herrmann JL.
Open Biol. 2016 Nov;6(11). pii: 160185.

Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking.

Bernut A, Nguyen-Chi M, Halloum I, Herrmann JL, Lutfalla G, Kremer L.
PLoS Pathog. 2016 Nov 2;12(11):e1005986. doi: 10.1371/journal.ppat.1005986. eCollection 2016

A unique PE_PGRS protein inhibiting host cell cytosolic defenses and sustaining full virulence of Mycobacterium marinum in multiple hosts.

Singh VK, Berry L, Bernut A, Singh S, Carrère-Kremer S, Viljoen A, Alibaud L, Majlessi L, Brosch R, Chaturvedi V, Geurtsen J, Drancourt M, Kremer L.
Cell Microbiol. 2016 Nov;18(11):1489-1507. doi: 10.1111/cmi.12606.

Experimental Models of Foamy Macrophages and Approaches for Dissecting the Mechanisms of Lipid Accumulation and Consumption during Dormancy and Reactivation of Tuberculosis.

Santucci P, Bouzid F, Smichi N, Poncin I, Kremer L, De Chastellier C, Drancourt M, Canaan S.
Front Cell Infect Microbiol. 2016 Oct 7;6:122. eCollection 2016. Review.

Identification of KasA as the cellular target of an anti-tubercular scaffold.

Abrahams KA, Chung CW, Ghidelli-Disse S, Rullas J, Rebollo-López MJ, Gurcha SS, Cox JA, Mendoza A, Jiménez-Navarro E, Martínez-Martínez MS, Neu M, Shillings A, Homes P, Argyrou A, Casanueva R, Loman NJ, Moynihan PJ, Lelièvre J, Selenski C, Axtman M, Kremer L, Bantscheff M, Angulo-Barturen I, Izquierdo MC, Cammack NC, Drewes G, Ballell L, Barros D, Besra GS, Bates RH.
Nat Commun. 2016 Sep 1;7:12581. doi: 10.1038/ncomms12581.

MAB_3551c encodes the primary triacylglycerol synthase involved in lipid accumulation in Mycobacterium abscessus.

Viljoen A, Blaise M, de Chastellier C, Kremer L.
Mol Microbiol. 2016 Nov;102(4):611-627. doi: 10.1111/mmi.13482.

MgtC as a Host-Induced Factor and Vaccine Candidate against Mycobacterium abscessus Infection.

Le Moigne V, Belon C, Goulard C, Accard G, Bernut A, Pitard B, Gaillard JL, Kremer L, Herrmann JL, Blanc-Potard AB.
Infect Immun. 2016 Sep 19;84(10):2895-903. doi: 10.1128/IAI.00359-16.

Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent.

Halloum I, Carrère-Kremer S, Blaise M, Viljoen A, Bernut A, Le Moigne V, Vilchèze C, Guérardel Y, Lutfalla G, Herrmann JL, Jacobs WR Jr, Kremer L.
Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4228-37. doi: 10.1073/pnas.1605477113.

Mycobacterium lutetiense sp. nov., Mycobacterium montmartrense sp. nov. and Mycobacterium arcueilense sp. nov., members of a novel group of non-pigmented rapidly growing mycobacteria recovered from a water distribution system.

Konjek J, Souded S, Guerardel Y, Trivelli X, Bernut A, Kremer L, Welte B, Joyeux M, Dubrou S, Euzeby JP, Gaillard JL, Sapriel G, Heym B.
Int J Syst Evol Microbiol. 2016 Sep;66(9):3694-3702. doi: 10.1099/ijsem.0.001253.

A new piperidinol derivative targeting mycolic acid transport in Mycobacterium abscessus.

Dupont C, Viljoen A, Dubar F, Blaise M, Bernut A, Pawlik A, Bouchier C, Brosch R, Guérardel Y, Lelièvre J, Ballell L, Herrmann JL, Biot C, Kremer L.
Mol Microbiol. 2016 Aug;101(3):515-29. doi: 10.1111/mmi.13406.

Use of the Salmonella MgtR peptide as an antagonist of the Mycobacterium MgtC virulence factor.

Belon C, Rosas Olvera M, Vives E, Kremer L, Gannoun-Zaki L, Blanc-Potard AB.
Future Microbiol. 2016;11(2):215-25. doi: 10.2217/fmb.15.134.

Insights into the smooth-to-rough transitioning in Mycobacterium bolletii unravels a functional Tyr residue conserved in all mycobacterial MmpL family members.

Bernut A, Viljoen A, Dupont C, Sapriel G, Blaise M, Bouchier C, Brosch R, de Chastellier C, Herrmann JL, Kremer L.
Mol Microbiol. 2016 Mar;99(5):866-83. doi: 10.1111/mmi.13283.

2015

Deciphering and Imaging Pathogenesis and Cording of Mycobacterium abscessus in Zebrafish Embryos.

Bernut A, Dupont C, Sahuquet A, Herrmann JL, Lutfalla G, Kremer L.
J Vis Exp.
2015 Sep 9;(103). doi: 10.3791/53130.

Looking through zebrafish to study host-pathogen interactions.

Bernut A, Lutfalla G, Kremer L.
Med Sci (Paris). 2015 Jun-Jul;31(6-7):638-46. doi: 10.1051/medsci/20153106017.

A new dehydratase conferring innate resistance to thiacetazone and intra-amoebal survival of Mycobacterium smegmatis.

Carrère-Kremer S, Blaise M, Singh VK, Alibaud L, Tuaillon E, Halloum I, van de Weerd R, Guérardel Y, Drancourt M, Takiff H, Geurtsen J, Kremer L.
Mol Microbiol. 2015 Jun;96(5):1085-102. doi: 10.1111/mmi.12992.

β-Lactamase inhibition by avibactam in Mycobacterium abscessus.

Dubée V, Bernut A, Cortes M, Lesne T, Dorchene D, Lefebvre AL, Hugonnet JE, Gutmann L, Mainardi JL, Herrmann JL, Gaillard JL, Kremer L, Arthur M.
J Antimicrob Chemother. 2015 Apr;70(4):1051-8. doi: 10.1093/jac/dku510.

National

- Y. Guérardel, UMR 8576, Université des Sciences et Technologies de Villeneuve d’Ascq

- S. Canaan, CNRS UPR 9025, Marseille

- M. Drancourt, Faculté de Médecine de la Timone, Marseille

- J-L. Herrmann, Université de Versailles Saint Quentin, Montigny le Bretonneux

-M. Arthur & JL Mainardi, Centre de Recherche des Cordeliers, UMRS 1138, Paris

-R. Brosch, Institut Pasteur, Paris

International

-J. Dziadek, Polish Academy of Sciences, Lodz, Poland.

-G. Coxon, University of Strathclyde, Glasgow, UK.

-A. Floto, University of Cambridge, UK

-W. R. Jacobs, Albert Einstein College of Medicine, NY.

-V. Kumar, Gura Nanak Dev University, Amritsar, India.

-R. Arancibia, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile

-H. Takiff, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.

-A. Kozikowski, University of Illinois at Chicago, USA

-K. Pethe, Nanyang Technological University Singapore, Singapore.

Team Members

Kremer Laurent (France) Research Director (DR1) -INSERM
Blaise Mickaël (France) Permanent researcher (CRCN)-CNRS
Daher Wassim (Lebanon) Permanent researcher (CRCN)-INSERM
Baneres-Roquet Françoise (Belgium) Engineer-CNRS
Viljoen Albertus (South-Africa) PostDoc
Dupont Christian (France) PostDoc
Johansen Matt (Australia) Postdoc 
Richard Matthias (France) PhD student
Tanja Küssau (Germany) PhD student
Gutierrez Ana Victoria (Venezuela) PhD student
Raynaud Clement (France) PhD student
UNG Kien Lam (Vietnam) PhD student


The team as in december 2017

Team Leader


Kremer Laurent

DR1 INSERM
HDR

More infos




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At a glance

Model organisms

Mycobacterium
Danio rerio
(zebrafish)


Biological process studied
The mycobacterial cell wall: its role in the pathophysiology of the infection, in the development of new therapeutic molecules and in resistance to antibiotics.

Techniques used
Microbiology
Genetics
Animal experimentation (zebrafish)
Cellular biology
Biochemistry
Structural Biology

Medical applications
Antimycobacterial drug discovery and development


 

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Fundings

        
        
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Contact


     
       

   

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IRIM
Institut de Recherche en Infectiologie de Montpellier
UMR 9004 - CNRS / UM
1919 route de Mende - 34293 Montpellier cedex 5
FRANCE

 

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