Abstract
Vancomycin (VAN) is unable to penetrate the outer membrane of Gram-negative bacteria and reach the target site. One approach to overcome this limitation is to associate it with compounds with permeabilizing or antimicrobial properties. Eudragit E100® (Eu) is a cationic polymer insufficiently characterized for its potential antimicrobial action. Eu-VAN combinations were characterized, the antimicrobial efficacy against Pseudomonas aeruginosa was evaluated and previous studies on the effects of Eu on bacterial envelopes were extended. Time-kill assays showed eradication of P. aeruginosa within 3–6 h exposure to Eu-VAN, whilst VAN was ineffective. Eu showed regrowth in 24 h and delayed colony pigmentation. Although permeabilization of bacterial envelopes or morphological alterations observed by TEM and flow cytometry after exposure to Eu were insufficient to cause bacterial death, they allowed access of VAN to the target site, since Eu-VAN/Van-FL-treated cultures showed fluorescent staining in all bacterial cells, indicating Van-FL internalization. Consequently, Eu potentiated the activity of an otherwise inactive antibiotic against P. aeruginosa. Moreover, Eu-VAN combinations exhibited improved physicochemical properties and could be used in the development of therapeutic alternatives in the treatment of bacterial keratitis.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
MC, LC and VR would like to thank CONICET- Argentina for scholarships. The authors especially thank Dr. Paul Hobson, native speaker, for revising the manuscript. They also thank Dr. Santiago Palma for providing useful suggestions.
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This work was supported by grants from Secretaria de Ciencia y Tecnología- Universidad Nacional de Córdoba (Res No 411/18); and FONCyT-Agencia Nacional de Promoción de la Investigación, Desarrollo Tecnológico e Innovación (PICT2012-0173).
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MC, LC and VR designed the protocols, carried out the experimental part and analyzed data. SG contributed in TEM image acquisition and analysis. MC drafted the manuscript with FA. FA conceived the study, acquired funding and resources, supervised the design of experiments and data interpretation, and completed the writing of the manuscript.
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Corti, M.B., Campagno, L.P., Romero, V.L. et al. Cationic polymer contributes to broaden the spectrum of vancomycin activity achieving eradication of Pseudomonas aeruginosa. Arch Microbiol 204, 507 (2022). https://doi.org/10.1007/s00203-022-03117-z
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DOI: https://doi.org/10.1007/s00203-022-03117-z