TURRITOXIN PAIAA SOURCE OF NOVEL ANTIMICROBIAL PEPTIDES AGAINST A. BAUMANNII

Antimicrobial Resistance (AMR) has been a silent pandemic. Newer antibiotics are required to treat drug-resistant pathogens. Antimicrobial peptides (AMPs) are promising next-generation antibiotics that are naturally produced in all living organisms. They are crucial components of the natural resistance framework of an organism. Small cationic peptides of 10-60 amino acid lengths have been successfully used as antibiotics. Marine ecosystems have an immense diversity of organisms and microorganisms that interact with each other, and thus have unique defense mechanisms. Marine cone snails are an untapped source of small, cationic AMPs. These snails secrete various proteinaceous venoms to deal with predators and preys. These cone snail venoms remain unexplored for their potential as antimicrobial peptides. The structural analysis of the venomous protein, Turritoxin PaIAa, from cone snails showed a high content of amino acids commonly found in AMPs. However, it did not exhibit any antibacterial activity. This protein was further investigated by overlap fractionation to identify hidden antimicrobial and cell-penetrating peptides. The unique peptide stretches obtained from PaIAa were evaluated against the toppriority ESKAPE pathogens. All peptides were active against A. baumannii. All peptides had cell-penetrating properties. These AMP candidates also showed promising physical, physicochemical, and pharmacokinetic properties. The AMP candidates identied in this study can be further evaluated by in vitro and in vivo testing.