Peptidoglycan recognition proteins are a new class of human bactericidal proteins

J Biol Chem. 2006 Mar 3;281(9):5895-907. doi: 10.1074/jbc.M511631200. Epub 2005 Dec 14.

Abstract

Skin and mucous membranes come in contact with external environment and protect tissues from infections by producing antimicrobial peptides. We report that human peptidoglycan recognition proteins 3 and 4 (PGLYRP3 and PGLYRP4) are secreted as 89-115-kDa disulfide-linked homo- and heterodimers and are bactericidal against several pathogenic and nonpathogenic transient, but not normal flora, Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also bacteriostatic toward all other tested bacteria, which include Gram-negative bacteria and normal flora Gram-positive bacteria. PGLYRP3 and PGLYRP4 are also active in vivo and protect mice against experimental lung infection. In contrast to antimicrobial peptides, PGLYRPs kill bacteria by interacting with their cell wall peptidoglycan, rather than permeabilizing their membranes. PGLYRP3 and PGLYRP4 are expressed in the skin, eyes, salivary glands, throat, tongue, esophagus, stomach, and intestine. Thus, we have identified the function of mammalian PGLYRP3 and PGLYRP4, and show that they are a new class of bactericidal and bacteriostatic proteins that have different structures, mechanism of actions, and expression patterns than antimicrobial peptides.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism*
  • Bacterial Infections / prevention & control
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Tissue Distribution

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Carrier Proteins
  • Cytokines
  • PGLYRP1 protein, human
  • peptidoglycan recognition protein