Genome Mining and Structural Study of Cathelicidins Across Chiroptera Species

The authors explored the genomic landscape of bat cathelicidins, critical proteins in the vertebrate innate immune system, across 41 bat species, which are notable for their high microbial tolerance. An array of bioinformatics tools, complemented by manual mining, were used to identify the curated cathelicidin sequences. Particular attention was given to the fourth exon, which is responsible for generating the biologically active peptide. This comprehensive exploration led to the identification of 72 annotated complete cathelicidins, with 44 being newly discovered. These 72 complete cathelicidin sequences, along with 7 incomplete and 4 nonfunctional sequences, result in a total of 78 peptides, 53 of which were previously unknown. These bat cathelicidins are characterized by a cathelicidin domain pfam00666, and the consensus sequence derived from aligning these domains shows a high degree of conservation in the position of each amino acid across all bat species, suggesting that they possess only one type of cathelicidin. Notably, the three-dimensional structure of the bat cathelicidin family domain closely resembles the cystatin domain previously described in <i>Sus scrofa</i> protegrin 3. The phylogenetic tree constructed using the bat conserved domain cluster species according to their taxonomic order, indicating the potential utility of this sequence as taxonomic markers. Finally, the authors propose a peptide classification based on three-dimensional structures and the presence or absence of the CAP18 domain, proline-rich or arginine-rich sequences. This approach holds great promise for future research focussed on precisely identifying antimicrobial peptides, conducting structure-activity and mechanism-of-action relationship studies and enhancing our understanding of the immune defence mechanisms in bats.