High-Content Screening of Raw Actinomycete Extracts for the Identification of Antituberculosis Activities

Heo, Jinyeong; Nam, Jiyoun; Jang, Jichan; Shum, David; Radu, Constantin; Cheng, Jinhua; Lee, Hanki; Suh, Joo‐Won; Delorme, Vincent

doi:10.1177/1087057116675887

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Resazurin was added to each well (0.02%, wt/vol), and the plates were analyzed at an excitation of 560 nm and emission of 590 nm. The percentage of growth inhibition was calculated using the RFU value, as described previously [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Pathogen Box screening for hit identification against Mycobacterium abscessus

et al. 2018

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Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. However, there is no official regimen for M. abscessus therapy. In this study, we screened the Pathogen Box, which contains 400 drug-like molecules active against neglected diseases, to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indicator of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, i.e., MMV688508, MMV688844, and MMV688845, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Among them, MMV688844 showed the best minimum inhibitory concentration value for not only wild-type M. abscessus but also for nine different R and S morphotype clinical isolates. Thus, we found that MMV688844, identified from the Pathogen Box screen, may be a promising candidate in the M. abscessus drug discovery pipeline.

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Section: Methodsmentioning

confidence: 99%

Pathogen Box screening for hit identification against Mycobacterium abscessus

et al. 2018

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“…Since 1940s, secondary metabolites and their associated derivatives have played a key role in anti-TB drugs development. This is best exemplified by an extremely active aminoglycoside, namely streptomycin, the first clinical drug that was made available against TB [67]. In a previous study, Streptocytosines A, Bamitecin and Amitecin isolated from sea water Streptomyces in Japan showed activity against M. smegmatis at 32, 16 and 8 µg/ml concentrations, respectively [68].…”

Section: Activity Against Planktonic Cultures Of M Tuberculosismentioning

confidence: 99%

Discovery of a novel antibiotic, Transitmycin, fromStreptomycessp unveils highly efficient activities against tuberculosis and human immunodeficiency virus

Kumar,

Ramasamy,

Doble

et al. 2024

Preprint

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HIV is identified as a factor that aggravates tuberculosis disease pathogenesis and its progression to latent TB. While, TB is declared as one of the major causes for AIDS-associated mortality. So there is a dire need for new drugs to combat such ailments that have a synergistic interaction.This has led us to study a novel antibiotic purified from a marine Streptomyces sp isolated from the coral reef ecosystem of South Indian coast. Streptomyces sp. R2 (MTCC 5597; DSM 26035)., isolated from the marine water was grown on agar plates and the crude yellowish orange pigment secreted was extracted using various solvents. The antibiotic, named as Transitmycin, was purified and tested against M. tuberculosis, drug resistant strains, and M. tuberculosis biofilm. The compound was also tested against HIV-1 viruses belonging to six subtypes. Several characterisation tools were used to elucidate the structure of this novel antibiotic. Transitmycin was derivitaised to elucidate the absolute configurations of the amino acids present in it. Tr, unlike actinomycin D, has L-valine in both the rings instead of D-valine (found in the latter). Also, one of the proline in Tr is in D–configuration while it is in L configuration in actinomycin D suggesting that ours is a novel compound and is not reported so far. It exhibits dual activities against the standard H37Rv, 49 drug sensitive clinical isolates, and MtB biofilm as well as standard and 20 clinical isolates of HIV. This is the first paper that reports the isolation of a new antibiotic from marine actinobacteria exhibiting unusual anti-TB and HIV activities which could be exploited further as a lead molecule in the quest for the design of drug with dual activities.

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Phenotypic Screening for Drug Discovery in Tuberculosis

Delorme

2020

Phenotypic Drug Discovery

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Tuberculosis is still a terrible human disease, killing over 1 million people every year worldwide. Better antibiotics that could shorten treatment duration and provide a relief to the emergence and spread of drug-resistant strains are definitely needed. In this chapter, we give an overview of the phenotypic screening systems available for drug discovery in tuberculosis, highlighting their potential strengths and weaknesses. In addition, we illustrate with examples how phenotypic screenings have contributed to the field, discuss the role they can play in the future and how some specific gaps could be addressed.

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High-Content Screening of Raw Actinomycete Extracts for the Identification of Antituberculosis Activities

Cited by 3 publications

References 29 publications

Pathogen Box screening for hit identification against Mycobacterium abscessus

Pathogen Box screening for hit identification against Mycobacterium abscessus

Discovery of a novel antibiotic, Transitmycin, fromStreptomycessp unveils highly efficient activities against tuberculosis and human immunodeficiency virus

Phenotypic Screening for Drug Discovery in Tuberculosis

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