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Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria

BACKGROUND: This study sought to develop new strategies for reverting the resistance of pathogenic Gram-negative bacilli by a combination of conventional antibiotics, potent permeabilizers and natural beta lactamase inhibitors enhancing the activity of various antibiotics. METHODS: The antibiotic su...

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Autores principales: Farrag, Hala A., Abdallah, Nagwa, Shehata, Mona M. K., Awad, Ebthag M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732830/
https://www.ncbi.nlm.nih.gov/pubmed/31500622
http://dx.doi.org/10.1186/s12929-019-0561-6
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author Farrag, Hala A.
Abdallah, Nagwa
Shehata, Mona M. K.
Awad, Ebthag M.
author_facet Farrag, Hala A.
Abdallah, Nagwa
Shehata, Mona M. K.
Awad, Ebthag M.
author_sort Farrag, Hala A.
collection PubMed
description BACKGROUND: This study sought to develop new strategies for reverting the resistance of pathogenic Gram-negative bacilli by a combination of conventional antibiotics, potent permeabilizers and natural beta lactamase inhibitors enhancing the activity of various antibiotics. METHODS: The antibiotic susceptibility in the presence of natural non-antibacterial tested concentrations of phytochemicals (permeabilizers and natural beta lactamase inhibitors) was performed by disk diffusion and susceptibility assays. Thymol and gallic acid were the most potent permeabilizers and facilitated the passage of the antibiotics through the outer membrane, as evidenced by their ability to cause LPS release, sensitize bacteria to SDS and Triton X-100. RESULTS: The combination of permeabilizers and natural beta lactamase inhibitors (quercetin and epigallocatechin gallate) with antibiotics induced greater susceptibility of resistant isolates compared to antibiotic treatment with beta lactamase inhibitors alone. Pronounced effects were detected with 24.4 Gy in vitro gamma irradiation on permeability barrier, beta lactamase activity, and outer membrane protein profiles of the tested isolates. CONCLUSIONS: The synergistic effects of the studied natural phytochemicals and antibiotics leads to new clinical choices via outer membrane destabilization (permeabilizers) and/or inactivation of the beta lactamase enzyme, which enables the use of older, more cost-effective antibiotics against resistant strains.
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spelling pubmed-67328302019-09-12 Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria Farrag, Hala A. Abdallah, Nagwa Shehata, Mona M. K. Awad, Ebthag M. J Biomed Sci Research BACKGROUND: This study sought to develop new strategies for reverting the resistance of pathogenic Gram-negative bacilli by a combination of conventional antibiotics, potent permeabilizers and natural beta lactamase inhibitors enhancing the activity of various antibiotics. METHODS: The antibiotic susceptibility in the presence of natural non-antibacterial tested concentrations of phytochemicals (permeabilizers and natural beta lactamase inhibitors) was performed by disk diffusion and susceptibility assays. Thymol and gallic acid were the most potent permeabilizers and facilitated the passage of the antibiotics through the outer membrane, as evidenced by their ability to cause LPS release, sensitize bacteria to SDS and Triton X-100. RESULTS: The combination of permeabilizers and natural beta lactamase inhibitors (quercetin and epigallocatechin gallate) with antibiotics induced greater susceptibility of resistant isolates compared to antibiotic treatment with beta lactamase inhibitors alone. Pronounced effects were detected with 24.4 Gy in vitro gamma irradiation on permeability barrier, beta lactamase activity, and outer membrane protein profiles of the tested isolates. CONCLUSIONS: The synergistic effects of the studied natural phytochemicals and antibiotics leads to new clinical choices via outer membrane destabilization (permeabilizers) and/or inactivation of the beta lactamase enzyme, which enables the use of older, more cost-effective antibiotics against resistant strains. BioMed Central 2019-09-09 /pmc/articles/PMC6732830/ /pubmed/31500622 http://dx.doi.org/10.1186/s12929-019-0561-6 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Farrag, Hala A.
Abdallah, Nagwa
Shehata, Mona M. K.
Awad, Ebthag M.
Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
title Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
title_full Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
title_fullStr Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
title_full_unstemmed Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
title_short Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
title_sort natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732830/
https://www.ncbi.nlm.nih.gov/pubmed/31500622
http://dx.doi.org/10.1186/s12929-019-0561-6
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