Proteomics

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Dissecting the antibacterial activity of Oxadiazolone-core derivatives against Mycobacterium abscessus


ABSTRACT: Mycobacterium abscessus is nowadays under the spotlight of the scientific community. This pathogenic mycobacteria is indeed responsible for a wide spectrum of infections involving mostly pulmonary infections in patients with cystic fibrosis. M. abscessus is intrinsically resistant to a broad range of antibiotics, including most antitubercular drugs, and is considered the most pathogenic and chemotherapy-resistant rapidly growing mycobacterium. Consequently, with very limited treatment options, the development of new therapeutic approaches to fight this pathogen are urgently needed. In this context, 19 oxadiazolone (OX) derivatives have been investigated for their antibacterial activity against both the rough (R) and smooth (S) variants of M. abscessus. Several OXs were active against extracellular M. abscessus growth with moderated minimal inhibitory concentrations (MIC), or intracellularly by inhibiting M. abscessus growth inside infected macrophages with MIC values similar to those of imipenem. Such promising results prompted us to identify the potential target enzymes of the sole extra and intracellular inhibitor of M. abscessus growth, i.e., iBpPPOX via activity-based protein profiling combined with mass spectrometry. This approach led to the identification of 21 potential protein candidates being mostly involved in M. abscessus lipid metabolism and/or in cell wall biosynthesis.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mycobacterium Abscessus

DISEASE(S): Cystic Fibrosis

SUBMITTER: Luc Camoin  

LAB HEAD: Luc Camoin

PROVIDER: PXD015680 | Pride | 2020-08-14

REPOSITORIES: Pride

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Publications

Dissecting the antibacterial activity of oxadiazolone-core derivatives against Mycobacterium abscessus.

Madani Abdeldjalil A   Mallick Ivy I   Guy Alexandre A   Crauste Céline C   Durand Thierry T   Fourquet Patrick P   Audebert Stéphane S   Camoin Luc L   Canaan Stéphane S   Cavalier Jean François JF  

PloS one 20200918 9


Mycobacterium abscessus (M. abscessus), a rapidly growing mycobacterium, is an emergent opportunistic pathogen responsible for chronic bronchopulmonary infections in individuals with respiratory diseases such as cystic fibrosis. Most treatments of M. abscessus pulmonary infections are poorly effective due to the intrinsic resistance of this bacteria against a broad range of antibiotics including anti-tuberculosis agents. Consequently, the number of drugs that are efficient against M. abscessus r  ...[more]

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