Assessing the antifungal activity of Latarcin-1 derived peptide LDP-NLS against Mucorales. (#270)
Mucormycosis is a rare but fatal infection caused by the fungi belonging to the order of Mucorales. Renal toxicity and resistance related to the last resort antifungal agent Amphotericin B demands for the novel and less cytotoxic therapeutics that are less likely to develop resistance. Antimicrobial peptides (AMPs) are a class of small peptides that are found in almost all organisms and have been widely studied for their activity against bacteria, fungi, and viruses. Our group has been working in developing antimicrobial peptides against various pathogens. LDP-NLS is one such peptide that has shown activity against various species of Mucorales (Rhizopus azygosporous, R. oryzae, Mucor indicus, Cunninghamella bertholletiae) and is non-toxic to mammalian cells. Following the establishment of its antifungal activity against Mucorales, we are further interested in understanding the mechanism of action of the peptide against fungal hyphae and spores. Time kill kinetics has been performed on spores to determine the killing time. LDP-NLS could inhibit hyphae elongation as well as killed already formed hyphae, as visualized using PI uptake. Morphological changes upon treatment were observed using scanning electron microscopy. Further, ROS production, apoptosis assay and interaction studies with ergosterol, an important sterol for fungal membrane integrity, are being carried out to understand the mechanism at molecular level.