Antitoxin control of optimal transcriptional repression in the atypical HigB–HigA toxin–antitoxin system from Proteus vulgaris
Year: 2025
Type: article
Abstract: 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.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkaf610
Institutions: Emory University, Pennsylvania State University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Awards: G102163711, G107546177, G1286251239, G1313983767, G1394151085, G155291834, G1664757510, Phase II SER-CAT Optimization: Acquisition of a next generation area detector, G2287611682, Molecular Basis of Ribosomal Frameshifting, G262962599, Mechanism of HigB-mediated ribosome-dependent mRNA degradation, G3075337988, G426311843, G498139845, Pixel Array Detector for Macromolecular Crystallography, G5387317844, G5607048534, G6848031779, G6918803902, G7583137537, TRAINING PROGRAM IN BIOCHEMISTRY, CELL AND DEVELOPMENT BIOLOGY, Antimicrobial Resistance and Therapeutic Discovery Training Program, Ribosome regulation, inhibition, and quality control mechanisms, Training Program in Biochemistry, Cell and Development Biology, NE-CAT: A Resource for Advanced Macromolecular Crystallography, Acquition of a microdiffractometer for SER-CAT, G969889393, G993149817
OpenAlex ID: W4412487649