Cyclipostins and Cyclophostin analogs as ...
Document type :
Article dans une revue scientifique: Article original
Title :
Cyclipostins and Cyclophostin analogs as promising compounds in the fight against tuberculosis
Author(s) :
Nguyen, Phuong Chi [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Delorme, Vincent [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Benarouche, Anaïs [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Martin, Benjamin [Auteur]
University of Missouri [St. Louis]
Paudel, Rishi [Auteur]
Gnawali, Giri [Auteur]
University of Missouri [St. Louis]
Madani, Abdeldjalil [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Puppo, Rémy [Auteur]
Institut de Microbiologie de la Méditerranée [IMM]
Landry, Valérie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Kremer, Laurent [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Brodin, Priscille [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Spilling, Christopher [Auteur]
University of Missouri [St. Louis]
Cavalier, Jean-François [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Canaan, Stéphane [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Delorme, Vincent [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Benarouche, Anaïs [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Martin, Benjamin [Auteur]
University of Missouri [St. Louis]
Paudel, Rishi [Auteur]
Gnawali, Giri [Auteur]
University of Missouri [St. Louis]
Madani, Abdeldjalil [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Puppo, Rémy [Auteur]
Institut de Microbiologie de la Méditerranée [IMM]
Landry, Valérie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Kremer, Laurent [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Brodin, Priscille [Auteur]

Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Spilling, Christopher [Auteur]
University of Missouri [St. Louis]
Cavalier, Jean-François [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Canaan, Stéphane [Auteur]
Enzymologie interfaciale et de physiologie de la lipolyse [EIPL]
Journal title :
Scientific Reports
Pages :
11751
Publisher :
Nature Publishing Group
Publication date :
2017
ISSN :
2045-2322
HAL domain(s) :
Sciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses
English abstract : [en]
A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of ...
Show more >A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC 50 = 500 nM). This compound was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 23 potential candidates, most of them being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA and HsaD, have previously been reported as essential for in vitro growth of M. tb and/or survival and persistence in macrophages. Overall, our findings support the assumption that CyC 17 may thus represent a novel class of multi-target inhibitor leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser-and Cys-containing enzymes participating in important physiological processes.Show less >
Show more >A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC 50 = 500 nM). This compound was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 23 potential candidates, most of them being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA and HsaD, have previously been reported as essential for in vitro growth of M. tb and/or survival and persistence in macrophages. Overall, our findings support the assumption that CyC 17 may thus represent a novel class of multi-target inhibitor leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser-and Cys-containing enzymes participating in important physiological processes.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Source :
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