Antitoxin control of optimal transcriptional repression in the atypical HigB-HigA toxin-antitoxin system from Proteus vulgaris.

Publication Type:

Journal Article

Authors:

Pavelich, Ian J; Schureck, Marc A; Srinivas, Pooja; Blackburn, Taylor M; Wang, Dongxue; Hoffer, Eric D; Boamah, Michelle; Zaldana, Kimberly; Onuoha, Nina; Miles, Stacey J; Grabowicz, Marcin; Okafor, C Denise; Dunham, Christine M

Source:

Nucleic Acids Res, Volume 53, Issue 13 (2025)

Keywords:

Antitoxins, Bacterial Proteins, Bacterial Toxins, DNA, Bacterial, Gene Expression Regulation, Bacterial, Molecular Dynamics Simulation, Operator Regions, Genetic, Plasmids, Promoter Regions, Genetic, Proteus vulgaris, Toxin-Antitoxin Systems, Transcription, Genetic

Abstract:

<p>Bacterial toxin-antitoxin (TA) pairs transcriptionally autoregulate their expression via a repression/derepression mechanism in response to changing environmental conditions. The structural diversity of TA systems influences the mechanisms of transcriptional regulation. Here, we define the molecular mechanism for the plasmid-encoded HigB-HigA TA pair originally identified in a post-operative infection with antibiotic-resistant Proteus vulgaris. We determine DNA binding and promoter activity by the HigB-HigA complex supported by structural biology and molecular dynamics simulations of an elusive DNA operator-TA repressor complex. To define the optimal oligomeric TA repressor-DNA operator complex required for derepression, we engineered a dedicated trimeric HigB-HigA2 complex that represses transcription more than 26-fold as compared to the tetrameric HigB2-HigA2. These results expand the known diversity of how the HigB-HigA TA family is autoregulated.</p>

PDB: 
9CHL, 9CHN
Detector: 
EIGER