10.1371/journal.pone.0197467 Johan A. Kers Johan A. Kers Anthony W. DeFusco Anthony W. DeFusco Jae H. Park Jae H. Park Jin Xu Jin Xu Mark E. Pulse Mark E. Pulse William J. Weiss William J. Weiss Martin Handfield Martin Handfield OG716: Designing a fit-for-purpose lantibiotic for the treatment of <i>Clostridium difficile</i> infections Public Library of Science 2018 substitution variants performer OG 716 lantibiotic Mutacin 1140 fit-for-purpose lantibiotic vivo testing novel antibiotics novel lantibiotic infections Lantibiotics MU 1140-derived variants novel mechanism CDI hamster model CDAD 3 weeks post infection biologically-relevant systems 2018-06-12 18:01:08 Dataset https://plos.figshare.com/articles/dataset/OG716_Designing_a_fit-for-purpose_lantibiotic_for_the_treatment_of_i_Clostridium_difficile_i_infections/6494786 <div><p>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 <i>C</i>. <i>difficile</i> 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 <i>in vitro</i> were further evaluated orally in the Golden Syrian hamster model of CDAD. <i>In vivo</i> 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.</p></div>