Tachypressin antimicrobial peptide from veterinary spiders with potent antifungal activity against Cryptococcus neoformans
abstract
Veterinary spider venoms have evolved into a diverse natural pharmacopoeia through selective pressures. Cryptococcus neoformans It is a global health threat that frequently causes life-threatening meningitis and fungemia, especially in immunocompromised patients. In this study, a new anti-C. neoformans QS18 (QCFKVCFRKRCFTKCSRS), a peptide derived from the venom gland of a spider native to China Chirobrachychis riboensis By utilizing bioinformatics tools. QS18 shares >50% sequence similarity with tachyplesin peptides previously identified only in horseshoe crab hemocytes, expanding the known repertoire of the tachyplesin family to terrestrial arachnids. Oxidative folding of QS18 significantly enhances its antifungal activity and stability, resulting in a minimum inhibitory concentration of 1.4 μM. The antibacterial mechanism of QS18 involves disruption of cell membranes. QS18 exhibits less than 5% hemolysis in human red blood cells, exhibiting microbial selectivity and a favorable safety profile for therapeutic applications. Additionally, mouse model studies highlight the ability of QS18 as an antifungal agent with significant anti-inflammatory activity. Our study demonstrates that QS18 is a promising template for spider venom peptide research as well as a novel candidate for peptide antifungal drug development.
