AI Article Synopsis

  • - Innate immunity in invertebrates provides effective antimicrobial peptides (AMPs) that combat drug-resistant infections, sparking interest in finding new β-hairpin AMPs from worm proteins with a BRICHOS domain.
  • - Researchers discovered new BRICHOS AMPs from caecilians, a lesser-known group of vertebrates, revealing similarities to lung surfactants and suggesting a unique lung function.
  • - The identified peptides show strong antibacterial properties against multidrug-resistant ESKAPE pathogens while being low in toxicity, indicating potential as a new antibiotic model and highlighting a previously unrecognized lung immunity mechanism.

Article Abstract

Innate immunity of invertebrates offers potent antimicrobial peptides (AMPs) against drug-resistant infections. To identify new worm β-hairpin AMPs, we explored the sequence diversity of proteins with a BRICHOS domain, which comprises worm AMP precursors. Strikingly, we discovered new BRICHOS AMPs not in worms, but in caecilians, the least studied clade of vertebrates. Two precursor proteins from Microcaecilia unicolor and Rhinatrema bivittatum resemble SP-C lung surfactants and bear worm AMP-like peptides at C-termini. The analysis of M. unicolor tissue transcriptomes shows that the AMP precursor is highly expressed in the lung along with regular SP-C, suggesting a different, protective function. The peptides form right-twisted β-hairpins, change conformation upon lipid binding, and rapidly disrupt bacterial membranes. Both peptides exhibit broad-spectrum activity against multidrug-resistant ESKAPE pathogens with 1-4 μM MICs and remarkably low toxicity, giving 40-70-fold selectivity towards bacteria. These BRICHOS AMPs, previously unseen in vertebrates, reveal a novel lung innate immunity mechanism and offer a promising antibiotics template.

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Source
http://dx.doi.org/10.1016/j.bbrc.2024.149913DOI Listing

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