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

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

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Gram-Negative Bacteria
Zinc
Peptides
Bacteria
Defensins
Sweat
Phospholipases A2
Gram-Positive Bacteria
Body Fluids
Glycosylation
Saliva
Innate Immunity
Mammals
Salts
Cell Membrane
peptidoglycan recognition protein
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides. / Wang, Minhui; Liu, Li Hui; Wang, Shiyong; Li, Xinna; Lu, Xiaofeng; Gupta, Dipika; Dziarski, Roman.

In: Journal of Immunology, Vol. 178, No. 5, 01.03.2007, p. 3116-3125.

Research output: Contribution to journalArticle

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