Zebrafish Peptidoglycan Recognition Proteins Are Bactericidal Amidases Essential for Defense against Bacterial Infections

Abstract

Peptidoglycan recognition proteins (PGRPs) are structurally conserved through evolution, but their functions in innate immunity are different in invertebrates and vertebrates. We asked what the functions of PGRPs in fish are and whether they are indispensable for defense against infection because fish are the first vertebrates that developed adaptive immunity, but they still rely solely on innate immunity during early development of embryos. We identified and cloned three zebrafish PGRPs and showed that they are highly expressed in eggs, developing embryos, and adult tissues that contact external environment. Zebrafish PGRPs have both peptidoglycan-lytic amidase activity and broad-spectrum bactericidal activity, which is a unique feature. Furthermore, we demonstrated that in the developing zebrafish embryo, one of these PGRPs is essential for defense and survival during bacterial infections. These data demonstrate an absolute requirement for innate immunity in defense against infections in fish embryos and for a PGRP protein for survival in vertebrates.

PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse’s offspring

“…6A). When Zn 2+ was removed from rec-protein by EGTA treatment, recPGRP-LB lost its bactericidal activity, in agreement with the human and zebrafish PGRPs (29,30). The bactericidal action of recPGRP-LB was dose-dependent with low concentrations (≤5 μg/mL) showing less killing activity (Fig.…”

Zebrafish peptidoglycan recognition protein SC (zfPGRP-SC) mediates multiple intracellular signaling pathways

“…In a previous study using morpholinos for PGLYRP-2 and PGLYRP-5 (equal to zfPGRP-SC), Li et al [16] found that the morpholino designed for blocking PGLYRP-5 inhibited specifically the translation of this protein; however, PGLYRP-2 could not be influenced by the injection of morpholino. Our results from siRNA were consistent with the reports from Li et al [16].…”

“…Recently, several PGRPs have been identified in lower vertebrates, namely teleost fish [6,16]. Zebrafish (Danio rerio) peptidoglycan recognition protein 5 (namely zfPGRP-SC) has been shown to have both amidase and bactericidal activities [16], and hence differs functionally from both insects and mammals.…”

“…Zebrafish (Danio rerio) peptidoglycan recognition protein 5 (namely zfPGRP-SC) has been shown to have both amidase and bactericidal activities [16], and hence differs functionally from both insects and mammals. To gain an insight into the evolution of the function of PGRP-SC in activation of Toll or TLR and in initiating signal transduction pathways or inducing proteolytic cascades, the signal pathways involved in the activation of TLRs were investigated by using real-time PCR, and the genome-wide expression profile was monitored by using highdensity oligonucleotide arrays in zebrafish embryos with RNAimediated knock-down of zfPGRP-SC.…”

Expression and functional characterization of PGRP6 splice variants in grass carp Ctenopharyngodon idella

“…However, vertebrates have a smaller number of PGRP genes; four genes including PGLYRP-1, PGLYRP-2, PGLYRP-3 and PGLYRP-4 exist in mammals (Liu et al, 2001) and three PGRPs including PGLYRP-2 (PGRP2), PGLYRP-5 (PGRP5) and PGLYRP-6 (PGRP6) in teleost fish Li et al, 2007). Based on the length of transcripts, PGRP genes are usually classified into short (S) and long forms (L).…”