The small DdrR protein directly interacts with the UmuDAb regulator of the mutagenic DNA damage response in Acinetobacter baumannii

Abstract

Acinetobacter baumannii poses a great threat in health care settings worldwide, with clinical isolates displaying an ever-evolving multidrug resistance. In strains of A. baumannii, expression of multiple error-prone polymerase genes are corepressed by UmuDAb, a member of the LexA superfamily, and a small protein, DdrR. It is currently unknown how DdrR establishes this repression. Here, we used surface plasmon resonance spectrometry to show that DdrR formed a stable complex with the UmuDAb regulator. Our results indicated that the carboxy-terminal dimerization domain of UmuDAb formed the interaction interface with DdrR. Our in vitro data also showed that RecA-mediated inactivation of UmuDAb was inhibited when this transcription factor was bound to its target DNA. In addition, we showed that DdrR interacted with a putative prophage repressor, homologous to LexA superfamily proteins. These data suggested that DdrR modulated DNA damage response and prophage induction in A. baumannii by binding to LexA-like regulators. IMPORTANCE We previously identified a 50-residue bacteriophage protein, gp7, which interacts with and modulates the function of the LexA transcription factor from Bacillus thuringiensis. Here, we present data that indicates that the small DdrR protein from A. baumannii likely coordinates the SOS response and prophage processes by also interacting with LexA superfamily members. We suggest that similar small proteins that interact with LexA-like proteins to coordinate DNA repair and bacteriophage functions may be common to many bacteria that mount the SOS response.

Publication DOI: https://doi.org/10.1128/jb.00601-21
Divisions: College of Health & Life Sciences > School of Biosciences
Additional Information: (c) 2022, American Society for Microbiology. All rights reserved. This is an accepted manuscript of an article accepted for publication in the Journal of Bacteriology. This work was funded by grants to MB and AP from the Slovenian Research Agency (J1-8150, P1-0207 and J4-1778) and DFB was generously supported by BBSRC grant BB/R017689/1.
Uncontrolled Keywords: Acinetobacter baumannii,DNA damage,DNA repair,Induction of gene expression,LexA UmuDAb,SOS response,antibiotic resistance,bacteriophage induction,Microbiology,Molecular Biology
Publication ISSN: 1098-5530
Full Text Link:
Related URLs: https://journal ... 128/jb.00601-21 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2022-03-15
Published Online Date: 2022-02-22
Authors: Pavlin, Anja
Bajc, Gregor
Fornelos, Nadine
Browning, Douglas F (ORCID Profile 0000-0003-4672-3514)
Butala, Matej

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Version: Accepted Version

Access Restriction: Restricted to Repository staff only until 22 August 2022.


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