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The use of 4-Hexylresorcinol as antibiotic adjuvant

Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhan...

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Autores principales: Nikolaev, Y. A., Tutel’yan, A. V., Loiko, N. G., Buck, J., Sidorenko, S. V., Lazareva, I., Gostev, V., Manzen’yuk, O. Y., Shemyakin, I. G., Abramovich, R. A., Huwyler, J., El’-Registan, G. I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508414/
https://www.ncbi.nlm.nih.gov/pubmed/32960928
http://dx.doi.org/10.1371/journal.pone.0239147
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author Nikolaev, Y. A.
Tutel’yan, A. V.
Loiko, N. G.
Buck, J.
Sidorenko, S. V.
Lazareva, I.
Gostev, V.
Manzen’yuk, O. Y.
Shemyakin, I. G.
Abramovich, R. A.
Huwyler, J.
El’-Registan, G. I.
author_facet Nikolaev, Y. A.
Tutel’yan, A. V.
Loiko, N. G.
Buck, J.
Sidorenko, S. V.
Lazareva, I.
Gostev, V.
Manzen’yuk, O. Y.
Shemyakin, I. G.
Abramovich, R. A.
Huwyler, J.
El’-Registan, G. I.
author_sort Nikolaev, Y. A.
collection PubMed
description Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR.
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spelling pubmed-75084142020-10-01 The use of 4-Hexylresorcinol as antibiotic adjuvant Nikolaev, Y. A. Tutel’yan, A. V. Loiko, N. G. Buck, J. Sidorenko, S. V. Lazareva, I. Gostev, V. Manzen’yuk, O. Y. Shemyakin, I. G. Abramovich, R. A. Huwyler, J. El’-Registan, G. I. PLoS One Research Article Ever decreasing efficiency of antibiotic treatment due to growing antibiotic resistance of pathogenic bacteria is a critical issue in clinical practice. The two generally accepted major approaches to this problem are the search for new antibiotics and the development of antibiotic adjuvants to enhance the antimicrobial activity of known compounds. It was therefore the aim of the present study to test whether alkylresorcinols, a class of phenolic lipids, can be used as adjuvants to potentiate the effect of various classes of antibiotics. Alkylresorcinols were combined with 12 clinically used antibiotics. Growth-inhibiting activity against a broad range of pro- and eukaryotic microorganisms was determined. Test organisms did comprise 10 bacterial and 2 fungal collection strains, including E. coli and S. aureus, and clinical isolates of K. pneumoniae. The highest adjuvant activity was observed in the case of 4-hexylresorcinol (4-HR), a natural compound found in plants with antimicrobial activity. 50% of the minimal inhibitory concentration (MIC) of 4-HR caused an up to 50-fold decrease in the MIC of antibiotics of various classes. Application of 4-HR as an adjuvant revealed its efficiency against germination of bacterial dormant forms (spores) and prevented formation of antibiotic-tolerant persister cells. Using an in vivo mouse model of K. pneumoniae-induced sepsis, we could demonstrate that the combination of 4-HR and polymyxin was highly effective. 75% of animals were free of infection after treatment as compared to none of the animals receiving the antibiotic alone. We conclude that alkylresorcinols such as 4-HR can be used as an adjuvant to increase the efficiency of several known antibiotics. We suggest that by this approach the risk for development of genetically determined antibiotic resistance can be minimized due to the multimodal mode of action of 4-HR. Public Library of Science 2020-09-22 /pmc/articles/PMC7508414/ /pubmed/32960928 http://dx.doi.org/10.1371/journal.pone.0239147 Text en © 2020 Nikolaev et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nikolaev, Y. A.
Tutel’yan, A. V.
Loiko, N. G.
Buck, J.
Sidorenko, S. V.
Lazareva, I.
Gostev, V.
Manzen’yuk, O. Y.
Shemyakin, I. G.
Abramovich, R. A.
Huwyler, J.
El’-Registan, G. I.
The use of 4-Hexylresorcinol as antibiotic adjuvant
title The use of 4-Hexylresorcinol as antibiotic adjuvant
title_full The use of 4-Hexylresorcinol as antibiotic adjuvant
title_fullStr The use of 4-Hexylresorcinol as antibiotic adjuvant
title_full_unstemmed The use of 4-Hexylresorcinol as antibiotic adjuvant
title_short The use of 4-Hexylresorcinol as antibiotic adjuvant
title_sort use of 4-hexylresorcinol as antibiotic adjuvant
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508414/
https://www.ncbi.nlm.nih.gov/pubmed/32960928
http://dx.doi.org/10.1371/journal.pone.0239147
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