OG716: Designing a fit-for-purpose lantibiotic for the treatment of <i>Clostridium difficile</i> infections Johan A. Kers Anthony W. DeFusco Jae H. Park Jin Xu Mark E. Pulse William J. Weiss Martin Handfield 10.1371/journal.pone.0197467 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> 2018-06-12 18:01:08 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