PXD010255

PXD010255 is an original dataset announced via ProteomeXchange.

Title	Oxadiazolone derivatives against M. tuberculosis
Description	Oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against three pathogenic slow-growing mycobacteria: Mycobacterium marinum, Mycobacterium bovis BCG and the avirulent Mycobacterium tuberculosis (M. tb) mc26230. The encouraging MIC values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M. tb growth only with moderated MIC, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. One OX derivatives, HPOX, was selected and 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 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.
HostingRepository	PRIDE
AnnounceDate	2018-09-25
AnnouncementXML	Submission_2018-09-25_09:02:55.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luc Camoin
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-28 01:30:28	ID requested
⏵ 1	2018-09-25 09:02:56	announced

Nguyen PC, Delorme V, B, é, narouche A, Guy A, Landry V, Audebert S, Pophillat M, Camoin L, Crauste C, Galano JM, Durand T, Brodin P, Canaan S, Cavalier JF, Oxadiazolone derivatives, new promising multi-target inhibitors against M. tuberculosis. Bioorg Chem, 81():414-424(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Tuberculosis, Oxadiazolone, Lipolytic enzyme inhibitors, Activity-based probe (ABP)

Luc Camoin
contact affiliation	Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille Protéomique
contact email	luc.camoin@inserm.fr
lab head
Luc Camoin
contact affiliation	Life Sciences
contact email	luc.camoin@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010255
     1. Label: PRIDE project
     2. Name: Oxadiazolone derivatives against M. tuberculosis