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Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa

The outer membrane of Gram-negative bacteria functions as an impermeable barrier to foreign compounds. Thus, modulating membrane transport can contribute to improving susceptibility to antibiotics and efficiency of bioproduction reactions. In this study, the cellular uptake of hydrophobic and large-...

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Autores principales: Yamamoto, Kyosuke, Yamamoto, Nao, Ayukawa, Shotaro, Yasutake, Yoshiaki, Ishiya, Koji, Nakashima, Nobutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980104/
https://www.ncbi.nlm.nih.gov/pubmed/35379875
http://dx.doi.org/10.1038/s41598-022-09635-6
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author Yamamoto, Kyosuke
Yamamoto, Nao
Ayukawa, Shotaro
Yasutake, Yoshiaki
Ishiya, Koji
Nakashima, Nobutaka
author_facet Yamamoto, Kyosuke
Yamamoto, Nao
Ayukawa, Shotaro
Yasutake, Yoshiaki
Ishiya, Koji
Nakashima, Nobutaka
author_sort Yamamoto, Kyosuke
collection PubMed
description The outer membrane of Gram-negative bacteria functions as an impermeable barrier to foreign compounds. Thus, modulating membrane transport can contribute to improving susceptibility to antibiotics and efficiency of bioproduction reactions. In this study, the cellular uptake of hydrophobic and large-scaffold antibiotics and other compounds in Gram-negative bacteria was investigated by modulating the homolog expression of bamB encoding an outer membrane lipoprotein and tolC encoding an outer membrane efflux protein via gene deletion and gene silencing. The potential of deletion mutants for biotechnological applications, such as drug screening and bioproduction, was also demonstrated. Instead of being subjected to gene deletion, wild-type bacterial cells were treated with cell-penetrating peptide conjugates of a peptide nucleic acid (CPP-PNA) against bamB and tolC homologs as antisense agents. Results revealed that the single deletion of bamB and tolC in Escherichia coli increased the uptake of large- and small-scaffold hydrophobic compounds, respectively. A bamB-and-tolC double deletion mutant had a higher uptake efficiency for certain antibiotics and other compounds with high hydrophobicity than each single deletion mutant. The CPP-PNA treated E. coli and Pseudomonas aeruginosa cells showed high sensitivity to various antibiotics. Therefore, these gene deletion and silencing approaches can be utilized in therapeutic and biotechnological fields.
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spelling pubmed-89801042022-04-06 Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa Yamamoto, Kyosuke Yamamoto, Nao Ayukawa, Shotaro Yasutake, Yoshiaki Ishiya, Koji Nakashima, Nobutaka Sci Rep Article The outer membrane of Gram-negative bacteria functions as an impermeable barrier to foreign compounds. Thus, modulating membrane transport can contribute to improving susceptibility to antibiotics and efficiency of bioproduction reactions. In this study, the cellular uptake of hydrophobic and large-scaffold antibiotics and other compounds in Gram-negative bacteria was investigated by modulating the homolog expression of bamB encoding an outer membrane lipoprotein and tolC encoding an outer membrane efflux protein via gene deletion and gene silencing. The potential of deletion mutants for biotechnological applications, such as drug screening and bioproduction, was also demonstrated. Instead of being subjected to gene deletion, wild-type bacterial cells were treated with cell-penetrating peptide conjugates of a peptide nucleic acid (CPP-PNA) against bamB and tolC homologs as antisense agents. Results revealed that the single deletion of bamB and tolC in Escherichia coli increased the uptake of large- and small-scaffold hydrophobic compounds, respectively. A bamB-and-tolC double deletion mutant had a higher uptake efficiency for certain antibiotics and other compounds with high hydrophobicity than each single deletion mutant. The CPP-PNA treated E. coli and Pseudomonas aeruginosa cells showed high sensitivity to various antibiotics. Therefore, these gene deletion and silencing approaches can be utilized in therapeutic and biotechnological fields. Nature Publishing Group UK 2022-04-04 /pmc/articles/PMC8980104/ /pubmed/35379875 http://dx.doi.org/10.1038/s41598-022-09635-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yamamoto, Kyosuke
Yamamoto, Nao
Ayukawa, Shotaro
Yasutake, Yoshiaki
Ishiya, Koji
Nakashima, Nobutaka
Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa
title Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa
title_full Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa
title_fullStr Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa
title_full_unstemmed Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa
title_short Scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by Escherichia coli and Pseudomonas aeruginosa
title_sort scaffold size-dependent effect on the enhanced uptake of antibiotics and other compounds by escherichia coli and pseudomonas aeruginosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980104/
https://www.ncbi.nlm.nih.gov/pubmed/35379875
http://dx.doi.org/10.1038/s41598-022-09635-6
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