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

Kumar, V.; Ramsamy, B.; Doble, M.; Manikkam, R.; Hanna, L. E.; Arumugam, G. s.; DOmodharan, K.; Ganesan, S.; Dusthakeer, A.; Lucia, P.; A Saadhali, S.; John, S.; Nagamiah, S.; UCA, J.; M, R.; Safeeda, A.; S, S.

2024-04-05 infectious diseases
10.1101/2024.04.03.24305291 medRxiv
Show abstract

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. HighlightsO_LIA novel antibiotic was purified from a marine Streptomyces sp isolated from the coral reef of S. India C_LIO_LIPresence of L-valine, not observed in actinomycin D, and one of the proline in D configuration suggest that it is a novel structure not reported before C_LIO_LIIt exhibits activity against standard MtB strain as well as clinical isolates and drug resistance ones C_LIO_LIIt exhibits anti-HIV activity against several clinical isolates C_LI

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