OG716: Designing a fit-for-purpose lantibiotic for the treatment of <i>Clostridium difficile</i> infections

Published on 2018-06-12T18:01:08Z (GMT) by
<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>

Cite this collection

Kers, Johan A.; DeFusco, Anthony W.; Park, Jae H.; Xu, Jin; Pulse, Mark E.; Weiss, William J.; et al. (2018): OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections. PLOS ONE. Collection.