Antimicrobial peptides and proteins of the horse--insights into a well-armed organism

Abstract

Antimicrobial peptides play a pivotal role as key effectors of the innate immune system in plants and animals and act as endogenous antibiotics. The molecules exhibit an antimicrobial activity against bacteria, viruses, and eukaryotic pathogens with different specificities and potencies depending on the structure and amino-acid composition of the peptides. Several antimicrobial peptides were comprehensively investigated in the last three decades and some molecules with remarkable antimicrobial properties have reached the third phase of clinical studies. Next to the peptides themselves, numerous organisms were examined and analyzed regarding their repertoire of antimicrobial peptides revealing a huge number of candidates with potencies and properties for future medical applications. One of these organisms is the horse, which possesses numerous peptides that are interesting candidates for therapeutical applications in veterinary medicine. Here we summarize investigations and knowledge on equine antimicrobial peptides, point to interesting candidates, and discuss prospects for therapeutical applications.

Figure 1

Expression of equine antimicrobial peptides in different tissues of the horse. Expression was detected on the mRNA-level or the protein level, respectively, as indicated by superscript characters m and p. The picture "Internal organs of the horse" was provided with kind permission by Virbac (^© Virbac).

Figure 2

Comparison of mature NK-lysins and granulysin from farm animals. Primary structure alignment of mature NK-lysins from the horse and pig and granulysin from cattle. Conserved and semi-conserved amino-acid residues with similar properties are highlighted in light grey, cysteine residues in dark grey. Similar amino acids were defined as follows: (A, G); (S, T); (E, D); (R, K, H); (Q, N); (V, I, L, M); (Y, F); (W); (P); (C) [81]. The arrow indicates an additional cysteine residue only present in the equine sequence. Gaps introduced to maximize amino-acid alignments are indicated by hyphens. The percent similarity to equine NK-lysin is given at the end of the pig/cattle sequence.

Figure 3

Amino-acid sequence alignment of selected mammalian cathelicidin precursors. Equine cathelicidins are shown in bold letters. Conserved amino-acid residues are highlighted in grey. Mature peptides are underlined. The peptide structure of the mature peptides is given at the end of each sequence. The signal peptide (light grey) and the cathelin domain (dark grey) are indicated by lines on top of the sequence block. Species abbreviations: [ECA] = Equus caballus, [SSC] = Sus scrofa, [BTA] = Bos taurus, [HSA] = Homo sapiens, [OCU] = Oryctolagus cuniculus, [MMU] = Mus musculus.

Figure 4

Comparison of mature a-defensin amino-acid sequences of the horse. Sequences of a-defensin precursors that share 100% identity within the mature peptide were combined, e.g., DEFA1 and DEFA2 = DEFA1/2. Gaps introduced to maximize amino-acid alignments are indicated by hyphens. Conserved residues are highlighted: cysteine residues are colored red; arginine and glutamic acid, forming an intramolecular salt bridge, are colored light grey; glycine is marked in dark grey. Defensin-like peptides are shown in italics. Premature stop codons are indicated by asterisks. Numbers at the end of each sequence indicate the total number of amino acids followed by the net charge at pH 7.5. DEFA37L is not shown because of a premature stop codon in the propeptide.