title: Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides.
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 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.
authors.affiliation: Indiana University School of Medicine, Northwest Campus, 3400 Broadway, Gary, IN 46408, USA.
authors.forename: Minhui
authors.initials: M
authors.lastname: Wang
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Liu
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wang
authors.forename: Xinna
authors.initials: X
authors.lastname: Li
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lu
authors.forename: Dipika
authors.initials: D
authors.lastname: Gupta
authors.forename: Roman
authors.initials: R
authors.lastname: Dziarski
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D010455:Peptides; C118897:peptidoglycan recognition protein; D015032:Zinc; D002118:Calcium