Dual Antimicrobial and Antiproliferative Activity of TcPaSK Peptide Derived from a Tribolium castaneum Insect Defensin

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.

Variability of defensin genes from a Mexican endemic Triatominae: Triatoma (Meccus) pallidipennis (Hemiptera: Reduviidae)

Chagas disease remains a serious health problem for countries where the most common mode of transmission is infection contracted from the feces of a Triatominae insect vector. In México, 32 species of Triatoma have been identified; amongst them, Triatoma (Meccus) pallidipennis is an endemic species reported to have high percentages of infection with T. cruzi. Defensins, cysteine-rich cationic peptides, are a family of antimicrobial peptides (AMPs); the synthesis of these molecules is crucial for insect’s immune defense. In the present study, the genes encoding defensins in T. pallidipennis were sequenced with the purpose of identifying the variability of these genes in a Mexican vector of T. cruzi. We found 12 different genes encoding three mature peptides, all of which had the typical folding of a functional insect defensin. In this work two Defensins type 1 and one type 4 were identified. The pro-peptide domain was highly variable and the mature peptide was not. This is the first report focus on variability of defensins from an epidemiologically important Triatoma in Mexico.