TY - DATA T1 - OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections PY - 2018/06/12 AU - Johan A. Kers AU - Anthony W. DeFusco AU - Jae H. Park AU - Jin Xu AU - Mark E. Pulse AU - William J. Weiss AU - Martin Handfield UR - https://plos.figshare.com/articles/dataset/OG716_Designing_a_fit-for-purpose_lantibiotic_for_the_treatment_of_i_Clostridium_difficile_i_infections/6494786 DO - 10.1371/journal.pone.0197467 L4 - https://ndownloader.figshare.com/files/11941232 L4 - https://ndownloader.figshare.com/files/11941235 L4 - https://ndownloader.figshare.com/files/11941238 L4 - https://ndownloader.figshare.com/files/11941241 KW - substitution variants KW - performer KW - OG 716 KW - lantibiotic Mutacin 1140 KW - fit-for-purpose lantibiotic KW - vivo testing KW - novel antibiotics KW - novel lantibiotic KW - infections Lantibiotics KW - MU 1140-derived variants KW - novel mechanism KW - CDI KW - hamster model KW - CDAD KW - 3 weeks post infection KW - biologically-relevant systems N2 - Lantibiotics continue to offer an untapped pipeline for the development of novel antibiotics. We report here the discovery of a novel lantibiotic for the treatment of C. difficile infection (CDI). The leads were selected from a library of over 300 multiple substitution variants of the lantibiotic Mutacin 1140 (MU1140). Top performers were selected based on testing for superior potency, solubility, manufacturability, and physicochemical and/or metabolic stability in biologically-relevant systems. The best performers in vitro were further evaluated orally in the Golden Syrian hamster model of CDAD. In vivo testing ultimately identified OG716 as the lead compound, which conferred 100% survival and no relapse at 3 weeks post infection. MU1140-derived variants are particularly attractive for further clinical development considering their novel mechanism of action. ER -