Membrane Binding Properties of Bacillomycin-D Derivatives with Model Membranes Composed of Different Sterols

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

San Francisco

Congreso; Biophysical Society 62st Annual Meeting; 2018

Biophysical Society

Exploration of new antimicrobial agents and study of their mechanism of action are urgently required to address multidrug-resistant pathogens. Among the antimicrobial agents, lipopeptides are promising antibiotic agents which exhibit actions against a broad spectrum of pathogenic bacteria and fungi with surfactant or pore activity. The primary action of these lipopeptides is the permeabilization of cellular membranes. In the present work, we have examined the binding and permeabilizing ability of the Bacillomycin-D homologs such as Bacillomycin-C14 and C16 on model membranes composed by different concentration of sterols. Bacillomycin-D homologs are cyclic lipopeptides with seven a-amino acids and a b-amino fatty acid linked by an amide bond to the constituent amino acid residue. Here, we explored the capacity of Bacillomycin- C14, and C16 to form itself monolayers and the ability of them to insert into a monolayer of PC-cholesterol and PC-ergosterol through Langmuir monolayer studies. On the other hand, the binding efficiency of Bacillomycin analogs was studied by measuring the intrinsic fluorescence of the lipopeptides bound to liposomes of different composition. Further binding information was obtained by quenching experiments with acrylamide. The Stern-Volmer constants (Ksv) results suggest that lipopeptides have more membrane penetration in POPC LUVs than POPC: Cholesterol LUVs. As ergosterol itself is acting as a quencher for tyrosine, then binding affinity of LUVs of POPC: ergosterol could mislead the results. Results obtained from calcein release from liposomes treated with both lipopeptides indicate that lipopeptides are more active in liposomes composed by PC: ergosterol than in those composed by PC and PC:Cholesterol.