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YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression
YgfB-mediated β-lactam resistance was recently identified in multi drug resistant Pseudomonas aeruginosa. We show that YgfB upregulates expression of the β-lactamase AmpC by repressing the function of the regulator of the programmed cell death pathway AlpA. In response to DNA damage, the antitermina...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998450/ https://www.ncbi.nlm.nih.gov/pubmed/36894667 http://dx.doi.org/10.1038/s42003-023-04609-4 |
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author | Eggers, Ole Renschler, Fabian A. Michalek, Lydia Anita Wackler, Noelle Walter, Elias Smollich, Fabian Klein, Kristina Sonnabend, Michael S. Egle, Valentin Angelov, Angel Engesser, Christina Borisova, Marina Mayer, Christoph Schütz, Monika Bohn, Erwin |
author_facet | Eggers, Ole Renschler, Fabian A. Michalek, Lydia Anita Wackler, Noelle Walter, Elias Smollich, Fabian Klein, Kristina Sonnabend, Michael S. Egle, Valentin Angelov, Angel Engesser, Christina Borisova, Marina Mayer, Christoph Schütz, Monika Bohn, Erwin |
author_sort | Eggers, Ole |
collection | PubMed |
description | YgfB-mediated β-lactam resistance was recently identified in multi drug resistant Pseudomonas aeruginosa. We show that YgfB upregulates expression of the β-lactamase AmpC by repressing the function of the regulator of the programmed cell death pathway AlpA. In response to DNA damage, the antiterminator AlpA induces expression of the alpBCDE autolysis genes and of the peptidoglycan amidase AmpDh3. YgfB interacts with AlpA and represses the ampDh3 expression. Thus, YgfB indirectly prevents AmpDh3 from reducing the levels of cell wall-derived 1,6-anhydro-N-acetylmuramyl-peptides, required to induce the transcriptional activator AmpR in promoting the ampC expression and β-lactam resistance. Ciprofloxacin-mediated DNA damage induces AlpA-dependent production of AmpDh3 as previously shown, which should reduce β-lactam resistance. YgfB, however, counteracts the β-lactam enhancing activity of ciprofloxacin by repressing ampDh3 expression and lowering the benefits of this drug combination. Altogether, YgfB represents an additional player in the complex regulatory network of AmpC regulation. |
format | Online Article Text |
id | pubmed-9998450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99984502023-03-11 YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression Eggers, Ole Renschler, Fabian A. Michalek, Lydia Anita Wackler, Noelle Walter, Elias Smollich, Fabian Klein, Kristina Sonnabend, Michael S. Egle, Valentin Angelov, Angel Engesser, Christina Borisova, Marina Mayer, Christoph Schütz, Monika Bohn, Erwin Commun Biol Article YgfB-mediated β-lactam resistance was recently identified in multi drug resistant Pseudomonas aeruginosa. We show that YgfB upregulates expression of the β-lactamase AmpC by repressing the function of the regulator of the programmed cell death pathway AlpA. In response to DNA damage, the antiterminator AlpA induces expression of the alpBCDE autolysis genes and of the peptidoglycan amidase AmpDh3. YgfB interacts with AlpA and represses the ampDh3 expression. Thus, YgfB indirectly prevents AmpDh3 from reducing the levels of cell wall-derived 1,6-anhydro-N-acetylmuramyl-peptides, required to induce the transcriptional activator AmpR in promoting the ampC expression and β-lactam resistance. Ciprofloxacin-mediated DNA damage induces AlpA-dependent production of AmpDh3 as previously shown, which should reduce β-lactam resistance. YgfB, however, counteracts the β-lactam enhancing activity of ciprofloxacin by repressing ampDh3 expression and lowering the benefits of this drug combination. Altogether, YgfB represents an additional player in the complex regulatory network of AmpC regulation. Nature Publishing Group UK 2023-03-10 /pmc/articles/PMC9998450/ /pubmed/36894667 http://dx.doi.org/10.1038/s42003-023-04609-4 Text en © The Author(s) 2023 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Eggers, Ole Renschler, Fabian A. Michalek, Lydia Anita Wackler, Noelle Walter, Elias Smollich, Fabian Klein, Kristina Sonnabend, Michael S. Egle, Valentin Angelov, Angel Engesser, Christina Borisova, Marina Mayer, Christoph Schütz, Monika Bohn, Erwin YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression |
title | YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression |
title_full | YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression |
title_fullStr | YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression |
title_full_unstemmed | YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression |
title_short | YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression |
title_sort | ygfb increases β-lactam resistance in pseudomonas aeruginosa by counteracting alpa-mediated ampdh3 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998450/ https://www.ncbi.nlm.nih.gov/pubmed/36894667 http://dx.doi.org/10.1038/s42003-023-04609-4 |
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