Chicken antimicrobial peptides: Genome-wide identification and functional and structural analysis

Abstract

Scope and Method of Study: The purpose of the study is to identify novel antimicrobial peptides in chickens and characterize the functions and structures of a few selected peptides for their therapeutic potential. A genome-wide computational screen of the entire chicken genome has been used to identify novel chicken defensins and cathelicidins. Putatively mature cathelicidins, fowlicidin-1 and -2, were synthesized and evaluated for their antibacterial, cytolytic, and LPS-binding activities. The tertiary structure of fowlicidin-1 was determined by CD and NMR. Based on the tertiary structure of fowlicidin-1, a series of truncation and substitution analogs were synthesized and tested separately for their antibacterial, cytolytic, and LPS-binding activities.

A gene cluster containing thirteen different beta-defensin genes and a cluster containing three cathelicidin genes have been identified. The beta-defensin gene cluster is found to localize on the chromosome 3q3.5-q3.7 as well as a cluster on chromosome 2p containing three cathelicidin genes. Fowlicidin-1 and -2 were found to display potent and salt-independent activities against a wide range of bacteria, including resistant strains. Furthermore, both fowlicidins are capable of binding lipopolysaccharide (LPS) and neutralize its inflammatory effects. Fowlicidin-1 was revealed to be largely an alpha- helical peptide with a slight kink close to the center. A short peptide variant, namely fowlicidin-1(8-26), stands out with the highest therapeutic potential among all peptide analogs, and represents a safer and more attractive therapeutic candidate than the parent peptide.