Structural Basis of Pore Formation in the Mannose Phosphotransferase System by Pediocin PA-1

Appl Environ Microbiol. 2022 Feb 8;88(3):e0199221. doi: 10.1128/AEM.01992-21. Epub 2021 Dec 1.


Bacteriocins are ribosomally synthesized bacterial antimicrobial peptides that have a narrow spectrum of antibacterial activity against species closely related to the producers. Pediocin-like (or class IIa) bacteriocins (PLBs) exhibit antibacterial activity against several Gram-positive bacterial strains by forming pores in the cytoplasmic membrane of target cells with a specific receptor, the mannose phosphotransferase system (man-PTS). In this study, we report the cryo-electron microscopy structures of man-PTS from Listeria monocytogenes alone and its complex with pediocin PA-1, the first and most extensively studied representative PLB, at resolutions of 3.12 and 2.45 Å, respectively. The structures revealed that the binding of pediocin PA-1 opens the Core domain of man-PTS away from its Vmotif domain, creating a pore through the cytoplasmic membranes of target cells. During this process, the N-terminal β-sheet region of pediocin PA-1 can specifically attach to the extracellular surface of the man-PTS Core domain, whereas the C-terminal half penetrates the membrane and cracks the man-PTS like a wedge. Thus, our findings shed light on a design of novel PLBs that can kill the target pathogenic bacteria. IMPORTANCE Listeria monocytogenes is a ubiquitous microorganism responsible for listeriosis, a rare but severe disease in humans, who become infected by ingesting contaminated food products (i.e., dairy, meat, fish, and vegetables): the disease has a fatality rate of 33%. Pediocin PA-1 is an important commercial additive used in food production to inhibit Listeria species. The mannose phosphotransferase system (man-PTS) is responsible for the sensitivity of Listeria monocytogenes to pediocin PA-1. In this study, we report the cryo-EM structures of man-PTS from Listeria monocytogenes alone and its complex with pediocin PA-1 at resolutions of 3.12 and 2.45 Å, respectively. Our results facilitate the understanding of the mode of action of class IIa bacteriocins as an alternative to antibiotics.

Keywords: antibiotic resistance; antimicrobial peptides; bacteriocins; man-PTS; mannose phosphotransferase; pediocin PA-1; pediocin-like/class IIa bacteriocins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriocins* / metabolism
  • Cryoelectron Microscopy
  • Humans
  • Listeria monocytogenes* / metabolism
  • Mannose / metabolism
  • Pediocins / chemistry
  • Phosphoenolpyruvate Sugar Phosphotransferase System* / metabolism


  • Bacteriocins
  • Pediocins
  • pediocin PA-1
  • Phosphoenolpyruvate Sugar Phosphotransferase System
  • Mannose