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 journalArticlepeer-review

    1 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 languageEnglish (US)
    Article number254
    JournalCommunications Biology
    Volume6
    Issue number1
    DOIs
    StatePublished - Dec 2023

    Bibliographical note

    Publisher Copyright:
    © 2023, The Author(s).

    ASJC Scopus subject areas

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

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