THE EFFICACY OF VANCOMYCIN AGAINST Staphylococcus aureus IS ENHANCED BY THE ACTION OF A CATIONIC POLYMER

CORTI, MELISA BELÉN; ROMERO, VERÓNICA L; ALOVERO, FABIANA L.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019: SAIC, SAFE, SAB, SAP, AACYTAL, NANOMED-AR, HCS.; 2019

Sociedad Argentina de Farmacologia Experimental y otras Sociedades Argentinas en diversas áreas de Biociencia

Reports of occurrence of methicillin-resistant S.aureus (MRSA) strains with resistance to the few available drugs such as vancomycin (VAN), daptomycin, linezolid, tigecycline and teicoplanin, prompt the search for novel treatments options.The last decade has witnessed enormous research focused on cationic polymers for various alternative therapeutic applications. We have previously used EudragitE100 (Eu), a cationic polymer, as a carrier of ionizable drugs which exhibited changes in their physicochemical or biological properties. The antimicrobial efficacy of Eu-VAN (VAN-containing Eu aqueous dispersions) against MRSA was evaluated and studies were conducted to understand the mechanisms involved in the observed effects.Eu-VAN bactericidal activity was evaluated by killing curves. VAN and free-drug Eu were assayed for comparison purposes. Eu-VAN at 4xMIC of VAN caused 99.9% killing within 360 min and bacterial erradication was observed within 24 h, whereas VAN needed 4-fold higher concentration for the same efficacy. Free-drug polymer (Eu) exhibited limited antimicrobial activity as population of bacteria was still viable after 24 h. Eu produces switch in sign of superficial net charge in S.aureus (Z potential measure) and a concentration-dependent membrane depolarization as determined by flow cytometry using DiBAC4, a potential sensitive probe. In addition, morphological changes were observed and these were confirmed by TEM. Fluorescence Microscopy using a fluorescent conjugates of VAN (BODIPY-FL®) allowed to demonstrate increased binding of VAN to S.aureus when bacteria is treated with Eu-VAN as compared to free VAN. The difference was statically significant. The interaction of the cationic polymer with the bacterial cell led to improved antimicrobial efficacy of VAN. This result provides a feasible alternative to avoid or combat antimicrobial resistance. Therefore, more studies are needed to define its potential use.