Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides.
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 Zn(2+)-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 Zn(2+) can only be partially replaced by Ca(2+) for killing of Gram-positive bacteria but not for killing of Gram-negative bacteria. The bactericidal activity of PGLYRPs is salt insensitive and requires N-glycosylation of PGLYRPs. The LD(99) of PGLYRPs for Gram-positive and Gram-negative bacteria is 0.3-1.7 muM, 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 A(2), alpha- and beta-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 Zn(2+)-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria that are synergistic with antibacterial peptides.
Wang
Minhui
M
Indiana University School of Medicine, Northwest Campus, 3400 Broadway, Gary, IN 46408, USA.
Liu
Li-Hui
LH
Wang
Shiyong
S
Li
Xinna
X
Lu
Xiaofeng
X
Gupta
Dipika
D
Dziarski
Roman
R
D000900:Anti-Bacterial Agents / Q000819:agonists* / Q000276:immunology; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000819:agonists* / Q000737:chemistry / Q000276:immunology; D015169:Colony Count, Microbial; D004306:Dose-Response Relationship, Immunologic; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D010455:Peptides / Q000819:agonists* / Q000737:chemistry / Q000276:immunology; D015032:Zinc / Q000737:chemistry / Q000276:immunology*
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D010455:Peptides; C118897:peptidoglycan recognition protein; D015032:Zinc; D002118:Calcium