Interaction of antifungal cyclic lipopeptides with fungi and mammalian membrane model systems

SATHISHKUMAR MUNUSAMY; LEOBARDO SERRANO CARREON; AGUSTÍN LUNA BULBARELA; LAURA BAKÁS; SABINA MATÉ; ROMINA VAZQUEZ; VANESA HERLAX; CARLOS MUÑOZ-GARAY

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. XLVI Reunión Anual de la Sociedad Argentina de Biofísica (SAB); 2017

SAIC, SAIB, SAI, SAA, SAB, SAB (biología), SAFE, SAFIS, SAH, SAP

Bacillus subtilis is a potent biocontrol agentproducing a wide array of lipopeptides for the inhibition of fungal growth. Amongthem, Bacillomycin D homologues are amphiphilic cyclic peptides composed of sevenα-amino acids linked to a β-amino fatty acid that have antifungal activityagainst human and plant pathogens and also strong hemolytic activity. In orderto better understand these phenomena, we explored the interactions ofBacillomycin D analogs having C14 (BC14) and C16 (BC16) β-amino fatty acids withmembrane model systems. The surface activity of BC14 and BC16 was studied inlipid monolayers composed of (phosphatidylcholine (PC)/ergosterol (Erg) vs PC/cholesterol (Chol)) and ternarylipid mixtures as simplified models of fungi and mammalian cell membranes (PC/phosphatidylethanolamine(PE)/Erg vs PC/sphingomyelin (SM)/Chol).Surface pressure (π) measurements showed similar results for the interaction ofBC14 with the different lipid mixtures assayed, with critical surface pressures(πc) of ~30 mN/m. BC16 produced higher π increments than BC14 after itsinteraction with all the monolayer compositions tested at different initial π, beingthis feature more notorious in PC/Erg, PC/PE/Erg and also in PC/SM/Cholmonolayers for which the calculated πc values were of 44, 38 and 40 mN/m,respectively. In calcein release assays, BC16 showed higher disruptive effectsthan BC14, being both compounds more active on PC/Erg than PC/Chol vesicles. Insummary, results showed that BC14 and BC16 could interact with both fungi andmammalian-like model membranes. In all the systems studied, BC16 produced highereffects than BC14 indicating that the longer hydrocarbon chain in the β-aminofatty acid of BC16 favors the interaction of the lipopeptide with the membrane.This correlates with the higher biological activity ofthis compound in bioassays.Keywords: antifungallipopeptides, model membranes, peptide-lipid interactions.