Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides

Minhui Wang, Li Hui Liu, Shiyong Wang, Xinna Li, Xiaofeng Lu, Dipika Gupta, Roman Dziarski

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Mammals have four peptidoglycan recognition proteins (PGRPs or PGLYRPs), which are secreted innate immunity pattern recognition molecules with effector functions. In this study, we demonstrate that human PGLYRP-1, PGLYRP-3, PGLYRP-4, and PGLYRP-3:4 have Zn2+-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria at physiologic Zn 2+ concentrations found in serum, sweat, saliva, and other body fluids. The requirement for Zn2+ can only be partially replaced by Ca2+ for killing of Gram-positive bacteria but not for killing of Grain-negative bacteria. The bactericidal activity of PGLYRPs is salt insensitive and requires N-glycosylation of PGLYRPs. The LD99 of PGLYRPs for Gram-positive and Gram-negative bacteria is 0.3-1.7 μM, and killing of bacteria by PGLYRPs, in contrast to killing by antibacterial peptides, does not involve permeabilization of cytoplasmic membrane. PGLYRPs and antibacterial peptides (phospholipase A2, α- and β-defensins, and bactericidal permeability-increasing protein), at subbactericidal concentrations, synergistically kill Gram-positive and Gram-negative bacteria. These results demonstrate that PGLYRPs are a novel class of recognition and effector molecules with broad Zn2+-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria that are synergistic with antibacterial peptides.

Original languageEnglish (US)
Pages (from-to)3116-3125
Number of pages10
JournalJournal of Immunology
Volume178
Issue number5
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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