The early stage peptidoglycan biosynthesis Mur enzymes are antibacterial and antisporulation drug targets for recurrent Clostridioides difficile infection

Anaerobe. 2020 Feb:61:102129. doi: 10.1016/j.anaerobe.2019.102129. Epub 2019 Nov 21.

Abstract

Sporulation during Clostridioides difficile infection (CDI) contributes to recurrent disease. Cell division and sporulation both require peptidoglycan biosynthesis. We show C. difficile growth and sporulation is attenuated by antisenses to murA and murC or the MurA inhibitor fosfomycin. Thus, targeting the early steps of peptidoglycan biosynthesis might reduce the onset of recurrent CDI.

Keywords: Antibiotic drug-targets; Heat-resistant spore cortex; Mur ligases; Peptidoglycan.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / metabolism*
  • Anti-Bacterial Agents / pharmacology*
  • Clostridioides difficile / drug effects*
  • Clostridioides difficile / enzymology*
  • Clostridium Infections / drug therapy
  • Clostridium Infections / microbiology*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Bacterial
  • Humans
  • Peptidoglycan / biosynthesis*
  • Spores, Bacterial / drug effects
  • Spores, Bacterial / enzymology

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Peptidoglycan
  • Alkyl and Aryl Transferases
  • UDP-N-acetylglucosamine 1-carboxyvinyltransferase