Current developments in lantibiotic discovery for treating Clostridium difficile infection

Expert Opin Drug Discov. 2019 Jan;14(1):71-79. doi: 10.1080/17460441.2019.1549032. Epub 2018 Nov 27.

Abstract

Clostridium difficile is a major cause of healthcare-associated diarrhea linked to the misuse of antimicrobials and the corresponding deleterious impact they have on the protective microbiota of the gut. Resistance to agents used to treat C. difficile including metronizadole and vancomycin has been reported highlighting the need for novel agents. Lantibiotics represent a novel class of agents that many studies have highlighted as effective against C. difficile. Areas covered: In this review lantibiotics including nisin, actagardine, mersacidin, NAI-107 and MU-1140 that exhibit good activity against C.difficile, all of which are currently in the preclinical phase of investigation are discussed. The lantibiotic NVB302, which has completed phase I clinical trials for the treatment of C. difficile, is also described. Expert opinion: Lantibiotics represent promising candidates for the treatment of C. difficile infections due to their novel mode of action, which is thought to decrease the potential of resistance developing and the fact they often possess a less deleterious effect on the protective gut microbiota when compared to traditional agents. They are also extremely amenable to bioengineering approaches and the incorporation of synthetic biology to produce more potent variants.

Keywords: Clostridium; Lantibiotic; bioengineering; infection.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology*
  • Bacteriocins / administration & dosage
  • Bacteriocins / adverse effects
  • Bacteriocins / pharmacology*
  • Clostridioides difficile / drug effects
  • Clostridioides difficile / isolation & purification
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / microbiology
  • Drug Discovery / methods
  • Drug Resistance, Bacterial
  • Gastrointestinal Microbiome / drug effects
  • Humans

Substances

  • Anti-Bacterial Agents
  • Bacteriocins