OG716

Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections

Johan A. Kers, Anthony W. DeFusco, Jae H. Park, Jin Xu, Mark E. Pulse, William Weiss, Martin Handfield

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0197467
JournalPLoS ONE
Volume13
Issue number6
DOIs
StatePublished - 1 Jun 2018

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Clostridium Infections
Clostridium difficile
Clostridium
Bacteriocins
bacteriocins
infection
Lead compounds
Mesocricetus
relapse
Testing
Solubility
Libraries
solubility
mechanism of action
Substitution reactions
Pipelines
antibiotics
testing
Anti-Bacterial Agents
Recurrence

Cite this

Kers, J. A., DeFusco, A. W., Park, J. H., Xu, J., Pulse, M. E., Weiss, W., & Handfield, M. (2018). OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections. PLoS ONE, 13(6), [e0197467]. https://doi.org/10.1371/journal.pone.0197467
Kers, Johan A. ; DeFusco, Anthony W. ; Park, Jae H. ; Xu, Jin ; Pulse, Mark E. ; Weiss, William ; Handfield, Martin. / OG716 : Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections. In: PLoS ONE. 2018 ; Vol. 13, No. 6.
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OG716 : Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections. / Kers, Johan A.; DeFusco, Anthony W.; Park, Jae H.; Xu, Jin; Pulse, Mark E.; Weiss, William; Handfield, Martin.

In: PLoS ONE, Vol. 13, No. 6, e0197467, 01.06.2018.

Research output: Contribution to journalArticleResearchpeer-review

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