Characterization and expression studies of Gaduscidin-1 and Gaduscidin-2; paralogous antimicrobial peptide-like transcripts from Atlantic cod (Gadus morhua)

Differential expression and biological activity of two piscidin paralogues and a novel splice variant in Atlantic cod (Gadus morhua L.)

“…It is not uncommon to observe a decrease in expression of antimicrobial peptides and this does not preclude them as crucial host defence factors (reviewed in [24]). A similar 1.4-fold downregulation of pis1 (GAD-1) in head kidney of cod has been detected one day after immunostimulation with formalin-killed Aeromonas salmonicida [22]. Hybrid striped bass moronecidin transcripts in the intestine were also suppressed by Streptococcus iniae, while its levels were clearly up-regulated in blood, gills and head kidney [6].…”

“…It also indicates that pis1 is more similar to the ancestral gene than pis2, in accordance with their predicted structural properties, tissue distribution and regulation upon antigenic challenge. The opposite relationship between pis1 (gad-1) and pis2 (gad-2) was recently reported based upon analysis via a simple neighbour-joining tree [22]. This misleading conclusion is most probably due to intrinsic limitations of the single method used, since the neighbour-joining tree topology is strongly dependent on the evolution model assumed.…”

“…Moreover, using in silico approaches we have identified another pis paralogue in cod, which was termed piscidin-2 (pis2). This gene corresponds to gaduscidin-2, which has been reported by Browne et al [22] during the preparation of this manuscript. In the present paper, we have determined the gene structure of both pis1 and pis2 paralogues, identified a novel splice variant of pis2 and analysed their phylogenetic relationship and molecular evolution.…”

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

“…Gaduscidin-1 (gad-1) and gaduscidin-2 (gad-2) were AMPs identified in the Atlantic cod, Gadus morhua , and shown to be highly, constitutively expressed in immune-relevant tissues [94,95]. Low pH was found to enhance the activity of both peptides against Escherichia coli , which appeared to involve membrane interaction, but interestingly, although gad-1 and gad-2 were predominantly α-helical at neutral pH, acid conditions led to a large decrease in the levels of α-helicity possessed by these peptides [29].…”

“…In response, molecular dynamic simulation studies were undertaken and predicted that the number of sequential histidine pairs contained by gad-1 and gad-2 were important to their ability for membrane disruption [30]. These AMPs possess one and two of these histidine pairs respectively [94] and the N-terminal regions of both peptides, which included this motif, were preferentially located proximal to membrane channels with which gad-1 and gad-2 were associated [30]. Based on the topology of the peptide–lipid interactions mediating the formation of these channels, it was suggested that the antimicrobial action of gad-1 and gad-2 may involve the use of a disordered toroidal pore type mechanism of membrane disruption [30,99,100].…”