The inhibition of type I bacterial signal peptidase: Biological consequences and therapeutic potential

Bioorg Med Chem Lett. 2015 Nov 1;25(21):4761-4766. doi: 10.1016/j.bmcl.2015.07.072. Epub 2015 Jul 26.

Abstract

The general secretory pathway has long been regarded as a potential antibiotic drug target. In particular, bacterial type I signal peptidase (SPase) is emerging as a strong candidate for therapeutic use. In this review, we focus on the information gained from the use of SPase inhibitors as probes of prokaryote biology. A thorough understanding of the consequences of SPase inhibition and the mechanisms of resistance that arise are essential to the success of SPase as an antibiotic target. In addition to the role of SPase in processing secreted proteins, the use of SPase inhibitors has elucidated a previously unknown function for SPase in regulating cleavage events of membrane proteins.

Keywords: Antibiotic; Arylomycin; Protein secretion; SPase; Virulence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / enzymology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Molecular Conformation
  • Serine Endopeptidases / metabolism

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Membrane Proteins
  • Serine Endopeptidases
  • type I signal peptidase