YgfB increases β-lactam resistance in Pseudomonas aeruginosa by counteracting AlpA-mediated ampDh3 expression.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
10 03 2023
10 03 2023
Historique:
received:
05
07
2022
accepted:
17
02
2023
entrez:
9
3
2023
pubmed:
10
3
2023
medline:
14
3
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36894667
doi: 10.1038/s42003-023-04609-4
pii: 10.1038/s42003-023-04609-4
pmc: PMC9998450
doi:
Substances chimiques
Ciprofloxacin
5E8K9I0O4U
beta-Lactams
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
254Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : BO 1527/4-1
Informations de copyright
© 2023. The Author(s).
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