Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources

• Published in: ACS infectious diseases 2016-04, Vol.2 (4), p.294-301
• Main Authors: Grzelak, Edyta M, Hwang, Changhwa, Cai, Geping, Nam, Joo-Won, Choules, Mary P, Gao, Wei, Lankin, David C, McAlpine, James B, Mulugeta, Surafel G, Napolitano, José G, Suh, Joo-Won, Yang, Seung Hwan, Cheng, Jinhua, Lee, Hanki, Kim, Jin-Yong, Cho, Sang-Hyun, Pauli, Guido F, Franzblau, Scott G, Jaki, Birgit U
• Format: Article
• Language: English
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.5b00150

While natural products constitute an established source of lead compounds, the classical iterative bioassay-guided isolation process is both time- and labor-intensive and prone to failing to identify active minor constituents. (HP)­TLC-bioautography-MS/NMR, which combines cutting-edge microbiological, chromatographic, and spectrometric technologies, was developed to accelerate anti-tuberculosis (TB) drug discovery from natural sources by acquiring structural information at a very early stage of the isolation process. Using the avirulent, bioluminescent Mtb strain mc27000 luxABCDE, three variations of bioautography were evaluated and optimized for sensitivity in detecting anti-TB agents, including established clinical agents and new leads with novel mechanisms of action. Several exemplary applications of this approach to microbial extracts demonstrate its potential as a routine method in anti-TB drug discovery from natural sources.