Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides.
J Immunol
; 178(5): 3116-25, 2007 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-17312159
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-34 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.
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Colección:
01-internacional
Asunto principal:
Péptidos
/
Zinc
/
Proteínas Portadoras
/
Bacterias Gramnegativas
/
Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos