In silicocharacterization of cysteine-stabilized αβ defensins from neglected unicellular microeukaryotes

Abstract

AbstractBackgroundThe emergence of multi-resistant pathogens have increased dramatically in recent years, becoming a major public-health concern. Among other promising antimicrobial molecules with potential to assist in this worldwide struggle, cysteine-stabilized αβ (CS-αβ) defensins are attracting attention due their efficacy, stability, and broad spectrum against viruses, bacteria, fungi, and protists, including many known human pathogens.ResultsHere, 23 genomes of ciliated protists were screened and three CS-αβ defensins with a likely antifungal activity were identified and characterized using bioinformatics from two freshwater and culturable speciesLaurentiellasp. (LsAMP-1 and LsAMP-2) andEuplotes focardii(EfAMP-1). Although any potential cellular ligand could be predicted for LsAMP-2 and EfAMP-1; evidences from structural, molecular dynamics, and docking analyses suggest that LsAMP-1 may form stably associations with phosphatidylinositol 4,5-bisphosphates (PIP2), a phospholipid found on many eukaryotic cells, which could, in turn, represent an anchorage mechanism within plasma membrane of targeted cells.ConclusionThese data stress that more biotechnology-oriented studies should be conducted on neglected protists, such ciliates, which could become valuable sources of novel bioactive molecules for therapeutic uses.