Dataset Information

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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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]

PMID: 32946441

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Project description:The experiment was carried out during two vegetation seasons from 25th of April to 10th of September. Two Polish potato cultivars, the drought-tolerant Gwiazda and drought-sensitive Oberon were used. Selected tubers with transverse diameters of 3 - 4 cm were pre-sprouted for 2 weeks before planting. Plants were grown in a vegetation hall in pots filled with a thin layer of gravel on the bottom and the universal vegetable soil substrate ‘Hollas’ (Agaris Polska Ltd., Poland) produced from peat with the addition of chalk at a pH range of 5.5-6.5. Additionally, in phase 20 of the BBCH-scale of plant development, MIS-3 (Intermag) fertilizer was applied. Water content (WC) in volumetric basis in soil pots was measured according Black (1965). Weather conditions during the years of study were monitored using a Weather Campbell Station (Campbell Scientific Inc.) located in close proximity, and a thermohygrograph placed between pots. Meteorological data of air temperature, the photosynthetically active radiation, and humidity were comparable in the years of study and favorable for potato development. Three weeks after the initiation of the tuberisation phase (56 DAP), plants were divided into 3 groups, each consisting of 6 plants. The first group of plants was subjected to soil drought (remained without irrigation, day/night temperature 22°C/18°C), the second one to high temperature (day/night temperature 38°C/25°C) and the third one was watered according to needs and at optimal temperature (control plants, day/night temperature 22°C/18°C). Stress application lasted 14 days and finished at 70 DAP. During this period, plants were placed in phytotron equipped with six Hortilux Schreder Lamps with Philips light bulbs of 1600 W each. Air humidity was in the range 65-70%. WC under 14 days of soil drought reached 30% (v/v), and remained 80% (v/v) in control and high temperature conditions. During the recovery period, after 14 days of stress treatment, WC reached control levels. Plant root material for proteomic research was collected on the 14th day of stress treatment (70 DAP).

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