CONICET | Buscador de Institutos y Recursos Humanos

Exploration of new antimicrobial agents and study of theirmechanism of action areurgently required to address multidrug-resistant pathogens. Among the antimicrobial agents, lipopeptidesare promising antibiotic agents which exhibit actions against a broad spectrumof pathogenic bacteria and fungi with surfactant or pore activity. The primary action of these lipopeptides is thepermeabilization of cellular membranes. In the present work, we have examinedthe binding and permeabilizing ability of the Bacillomycin-D homologs such as Bacillomycin-C14 and C16 on model membranes composed by differentconcentration of sterols. Bacillomycin-D homologs are cyclic lipopeptides withseven a-aminoacids and a b-aminofatty acid linked by an amide bond to the constituent amino acid residue.Here, we explored the capacity of Bacillomycin- C14, and C16 to form itselfmonolayers and the ability of them to insert into amonolayer of PC-cholesterol and PC-ergosterol through Langmuir monolayer studies. On the other hand, the binding efficiency ofBacillomycin analogs was studied by measuringthe intrinsic fluorescence of the lipopeptides bound toliposomes of different composition. Further binding information wasobtained byquenching experiments with acrylamide. The Stern-Volmer constants (Ksv) resultssuggest that lipopeptides have more membrane penetration in POPCLUVs than POPC: Cholesterol LUVs. As ergosterol itself is acting asa quencherfor tyrosine, then binding affinity of LUVs of POPC: ergosterol couldmislead the results. Results obtained from calcein release from liposomestreatedwith both lipopeptides indicate that lipopeptides are more active in liposomescomposed by PC: ergosterol than in those composed by PC and PC:Cholesterol.