9H6C

Crystal structure of the E. coli F-plasmid VapBC toxin-antitoxin complex (VapB T3N)

9H6C の概要

• エントリーDOI: 10.2210/pdb9h6c/pdb
• 分子名称: tRNA(fMet)-specific endonuclease VapC, Antitoxin (2 entities in total)
• 機能のキーワード: vapbc, toxin-antitoxin, antibiotic tolerance, toxin
• 由来する生物種: Escherichia coli KLY; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 51530.29

構造登録者

Hollingshead, S.,McVicker, G.,Nielsen, M.R.,Zhang, Y.,Pilla, G.,Jones, R.A.,Thomas, J.C.,Johansen, S.E.H.,Exley, R.M.,Brodersen, D.E.,Tang, C.M. (登録日: 2024-10-24, 公開日: 2024-12-18, 最終更新日: 2025-02-12)

主引用文献

Hollingshead, S.,McVicker, G.,Nielsen, M.R.,Zhang, Y.,Pilla, G.,Jones, R.A.,Thomas, J.C.,Johansen, S.E.H.,Exley, R.M.,Brodersen, D.E.,Tang, C.M.
Shared mechanisms of enhanced plasmid maintenance and antibiotic tolerance mediated by the VapBC toxin:antitoxin system.
Mbio, 16:e0261624-e0261624, 2025

PubMed Abstract: Toxin:antitoxin (TA) systems are widespread in bacteria and were first identified as plasmid addiction systems that kill bacteria lacking a TA-encoding plasmid following cell division. TA systems have also been implicated in bacterial persistence and antibiotic tolerance, which can be precursors of antibiotic resistance. Here, we identified a clinical isolate of (CS14) with a remarkably stable pINV virulence plasmid; pINV is usually frequently lost from , but plasmid loss was not detected from CS14. We found that the plasmid in CS14 is stabilized by a single nucleotide polymorphism (SNP) in its TA system. VapBC TA systems are the most common Type II TA system in bacteria, and consist of a VapB antitoxin and VapC PIN domain-containing toxin. The plasmid stabilizing SNP leads to a Q12L substitution in the DNA-binding domain of VapB, which reduces VapBC binding to its own promoter, impairing autorepression. However, VapBC mediates high-level plasmid stabilization because VapB is more prone to degradation by Lon than wild-type VapB; this liberates VapC to efficiently kill bacteria that no longer contain a plasmid. Of note, mutations that confer tolerance to antibiotics in also map to the DNA-binding domain of VapBC encoded by the chromosomally integrated F plasmid. We demonstrate that the tolerance mutations also enhance plasmid stabilization by the same mechanism as VapB. Our findings highlight the links between plasmid maintenance and antibiotic tolerance, both of which can promote the development of antimicrobial resistance.

PubMed: 39704502
DOI: 10.1128/mbio.02616-24

実験手法

X-RAY DIFFRACTION (2.65 Å)