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Title: Efficacy of combinations of colistin with other antimicrobials involves membrane fluidity and efflux machinery
Author: Armengol, Eva
Domenech, O.
Fusté i Domínguez, Ester
Pérez-Guillén, I.
Borrell Hernández, Jordi
Sierra Ortigosa, Josep Maria
Viñas, Miquel
Keywords: Pèptids
Malalties bacterianes
Bacterial diseases
Issue Date: 11-Jul-2019
Publisher: Dove Medical Press
Abstract: Objective: Despite its use was abandoned several decades ago, the polycationic peptide colistin has become the last hope to treat severe infections caused by multidrug-resistant Gram-negative bacteria. Thus, the development of colistin resistance may seriously compromise the efficacy of treatment. Moreover, colistin has high toxicity being dose dependent. A potentially effective strategy to avoid resistance may be to combine colistin with other antimicrobials. This may help in the rescue of old antimicrobials and in reducing toxic undesired effects. Methods: Antimicrobial susceptibility determination, efflux machinery function measurements in different conditions and measurement of inhibition of the extrusion by colistin were performed. Moreover, modifications of anisotropy of the membranes by using fluorescent dyes was accomplished. Results: Sub-inhibitory concentrations of colistin have a synergistic effect with several antimicrobials that act intracellularly (targeting protein synthesis and DNA replication). This effect was demonstrated through the uptake increases of acridine orange. in Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumanii but also in an intrinsically colistin-resistant species as Serratia marcescens. Measurements of the anisotropy of bacterial membranes, as a measure of membrane fluidity, showed significant changes indicative of colistin activity. Conclusion: The alterations in the cellular efflux machinery that resulted in higher intracellular concentrations of acridine orange, and likely of other antimicrobials combined with data of membrane fluidity and measured synergism in vitro allow us to envisage the use of these combinations to fight infections caused by multidrug-resistant bacte
Note: Reproducció del document publicat a:
It is part of: Infection and Drug Resistance, 2019, vol. 12, p. 2031-2038
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ISSN: 1178-6973
Appears in Collections:Articles publicats en revistes (Infermeria de Salut Pública, Salut mental i Maternoinfantil)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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