Abstract
Antimicrobial peptides (AMPs) found in the innate immune system of a wide range of organisms might prove useful to fight infections, due to the reported slower development of resistance to AMPs. Increasing the cationicity and keeping moderate hydrophobicity of the AMPs have been described to improve antimicrobial activity. We previously found a peptide derived from the Tribolium castaneum insect defensin 3, exhibiting antrimicrobial activity against several human pathogens. Here, we analyzed the effect against Staphyloccocus aureus of an extended peptide (TcPaSK) containing two additional amino acids, lysine and asparagine, flanking the former peptide fragment in the original insect defensin 3 protein. TcPaSK peptide displayed higher antimicrobial activity against S. aureus, and additionally showed antiproliferative activity against the MDA-MB-231 triple negative breast cancer cell line. A SWATH proteomic analysis revealed the downregulation of proteins involved in cell growth and tumor progression upon TcPaSK cell treatment. The dual role of TcPaSK peptide as antimicrobial and antiproliferative agent makes it a versatile molecule that warrants exploration for its use in novel therapeutic developments as an alternative approach to overcome bacterial antibiotic resistance and to increase the efficacy of conventional cancer treatments.
Highlights
On the basis of the theoretical predictions of the physicochemical parameters that mainly determine the antimicrobial activity, we compared the properties of this insect’s defensin 3 (Tcdef3) peptide with those of an extended peptide (TcPaSK) that contained the two amino acid residues that flank Tcdef3 fragment in the defensin 3 sequence
We have analyzed the antimicrobial activity against S. aureus of the TcPaSK peptide derived from the T. casteneum insect defensin 3
Our results showed a significantly high antimicrobial activity due to its ability to disrupt the bacterial cell membrane confirmed by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) analyses
Summary
Increasing resistance to conventional antibiotics represents one of the most critical menaces to human health and has fostered the development of antimicrobial peptides (AMPs) as next-generation drugs to selectively combat pathogens. AMPs are key components of innate immunity, providing the first line of defense of eukaryotic organisms against diverse microbial infections [3]. Several structural families of AMPs from insects have been described, and novel AMPs are continuously being discovered [7]. Due to their potent antibacterial, antifungal and antiviral activities, insect peptides with antimicrobial activity have recently attracted increased attention as potential therapeutic agents for medical applications such as treatment of multidrug resistant bacterial infections [7]
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