Title :

Effects of Lipid-Lowering Drugs on Vancomycin Susceptibility of Mycobacteria

Author(s) :

Rens, Céline [Auteur]
Université libre de Bruxelles [ULB]
Laval, Françoise [Auteur]
Institut de pharmacologie et de biologie structurale [IPBS]
Daffé, Mamadou [Auteur]
Institut de pharmacologie et de biologie structurale [IPBS]
Denis, Olivier [Auteur]
Université libre de Bruxelles [ULB]
Frita, Rosangela [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Baulard, Alain [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wattiez, Ruddy [Auteur]
Université de Mons / University of Mons [UMONS]
Lefèvre, Philippe [Auteur]
Institute of Information and Communication Technologies, Electronics and Applied Mathematics [ICTEAM]
Fontaine, Véronique [Auteur]
Université Grenoble Alpes - UFR Médecine [UGA UFRM]

Journal title :

Antimicrobial Agents and Chemotherapy

Pages :

6193-6199

Publisher :

American Society for Microbiology

Publication date :

2016-10

ISSN :

0066-4804

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

ABSTRACT Tuberculosis is still a cause of major concern, partly due to the emergence of multidrug-resistant strains. New drugs are therefore needed. Vancomycin can target mycobacteria with cell envelope deficiency. In this ...
Show more >ABSTRACT Tuberculosis is still a cause of major concern, partly due to the emergence of multidrug-resistant strains. New drugs are therefore needed. Vancomycin can target mycobacteria with cell envelope deficiency. In this study, we used a vancomycin susceptibility assay to detect drugs hampering lipid synthesis in Mycobacterium bovis BCG and in Mycobacterium tuberculosis . We tested three drugs already used to treat human obesity: tetrahydrolipstatin (THL), simvastatin, and fenofibrate. Only vancomycin and THL were able to synergize on M. bovis BCG and on M. tuberculosis , although mycobacteria could also be inhibited by simvastatin alone. Lipid analysis allowed us to identify several lipid modifications in M. tuberculosis H37Rv treated with those drugs. THL treatment mainly reduced the phthiocerol dimycocerosate (PDIM) content in the mycobacterial cell wall, providing an explanation for the synergy, since PDIM deficiency has been related to vancomycin susceptibility. Proteomic analysis suggested that bacteria treated with THL, in contrast to bacteria treated with simvastatin, tried to recover, inducing, among other reactions, lipid synthesis. The combination of THL and vancomycin should be considered a promising solution in developing new strategies to treat multidrug-resistant tuberculosis.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL