PXD014255

PXD014255 is an original dataset announced via ProteomeXchange.

Title	Cyclipostins and Cyclophostin analogs impair growth of Mycobacterium abscessus by inhibiting enzymes involved in many physiological processes
Description	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. 38 new analogs of Cyclipostins & Cyclophostin (CyC), compounds naturally produced by Streptomyces species, have been synthesized. Their antibacterial activities against clinical isolates belonging to the M. chelonae-abscessus clade, as well as Gram-negative and Gram-positive bacteria have been evaluated by the REMA method. The intracellular activities of the CyC against intramacrophagic M. abscessus have also been investigated and compared to those of imipenem. The CyCs displayed very low toxicity towards host cells and their inhibitory activity was exclusively restricted to mycobacteria. The best candidate, CyC17, showed a high selectivity for mycobacteria with MIC values (<2 up to 40 µg/mL) comparable to those of most classical antibiotics used to treat M. abscessus infections. Of importance, several CyCs were active against extracellular M. abscessus growth (i.e., CyC17 / CyC18β / CyC25 / CyC26) or against intracellular mycobacteria inside macrophages (i.e., CyC7α,β / CyC8α,β) with MIC values similar to or better than those of standard antibiotics. Based on these results, we intended to identify the potential target enzymes of CyC17/CyC26 in M. abscessus by activity-based protein profiling (ABPP) approach coupled with mass spectrometry differential analysis.
HostingRepository	PRIDE
AnnounceDate	2019-09-30
AnnouncementXML	Submission_2019-09-30_03:18:29.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; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-14 01:29:49	ID requested
⏵ 1	2019-09-30 03:18:31	announced

Madani A, Ridenour JN, Martin BP, Paudel RR, Abdul Basir A, Le Moigne V, Herrmann JL, Audebert S, Camoin L, Kremer L, Spilling CD, Canaan S, Cavalier JF, . ACS Infect Dis, 5(9):1597-1608(2019) [pubmed]

submitter keyword: Total synthesis

drug susceptibility

activity based-protein profiling

proteomics analysis, anti-mycobacterial agents

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. PXD014255
     1. Label: PRIDE project
     2. Name: Cyclipostins and Cyclophostin analogs impair growth of Mycobacterium abscessus by inhibiting enzymes involved in many physiological processes