YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression

Ole Eggers; Fabian A. Renschler; Lydia Anita Michalek; Noelle Wackler; Elias Walter; Fabian Smollich; Kristina Klein; Michael S. Sonnabend; Valentin Egle; Angel Angelov; Christina Engesser; Marina Borisova; Christoph Mayer; Monika Schütz; Erwin Bohn

doi:10.1038/s42003-023-04609-4

YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression

Ole Eggers, Fabian A. Renschler, Lydia Anita Michalek, Noelle Wackler, Elias Walter, Fabian Smollich, Kristina Klein, Michael S. Sonnabend, Valentin Egle, Angel Angelov, Christina Engesser, Marina Borisova, Christoph Mayer, Monika Schütz, Erwin Bohn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English (US)
Article number	254
Journal	Communications Biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-04609-4
State	Published - Dec 2023

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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10.1038/s42003-023-04609-4

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Eggers, O., Renschler, F. A., Michalek, L. A., Wackler, N., Walter, E., Smollich, F., Klein, K., Sonnabend, M. S., Egle, V., Angelov, A., Engesser, C., Borisova, M., Mayer, C., Schütz, M., & Bohn, E. (2023). YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression. Communications Biology, 6(1), Article 254. https://doi.org/10.1038/s42003-023-04609-4

@article{17479209f007492eb8e1e11c59220095,

title = "YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression",

abstract = "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.",

author = "Ole Eggers and Renschler, {Fabian A.} and Michalek, {Lydia Anita} and Noelle Wackler and Elias Walter and Fabian Smollich and Kristina Klein and Sonnabend, {Michael S.} and Valentin Egle and Angel Angelov and Christina Engesser and Marina Borisova and Christoph Mayer and Monika Sch{\"u}tz and Erwin Bohn",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s42003-023-04609-4",

language = "English (US)",

volume = "6",

journal = "Communications Biology",

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Eggers, O, Renschler, FA, Michalek, LA, Wackler, N, Walter, E, Smollich, F, Klein, K, Sonnabend, MS, Egle, V, Angelov, A, Engesser, C, Borisova, M, Mayer, C, Schütz, M & Bohn, E 2023, 'YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression', Communications Biology, vol. 6, no. 1, 254. https://doi.org/10.1038/s42003-023-04609-4

TY - JOUR

T1 - YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression

AU - Eggers, Ole

AU - Renschler, Fabian A.

AU - Michalek, Lydia Anita

AU - Wackler, Noelle

AU - Walter, Elias

AU - Smollich, Fabian

AU - Klein, Kristina

AU - Sonnabend, Michael S.

AU - Egle, Valentin

AU - Angelov, Angel

AU - Engesser, Christina

AU - Borisova, Marina

AU - Mayer, Christoph

AU - Schütz, Monika

AU - Bohn, Erwin

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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DO - 10.1038/s42003-023-04609-4

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SN - 2399-3642

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JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 254

ER -

YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression

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