ArticleScience advances2025
Multistate kinetics of the syringe-like injection mechanism of Tc toxins.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Advances in EPR Approaches for Studying Structural Properties of Membrane Proteins.Magnetic resonance in chemistry : MRC · 2026Review
- Protocol for preparing and characterizing samples for combined microsecond freeze-hyperquenching and electron paramagnetic resonance spectroscopy.STAR protocols · 2026Article
- Complete structures of the YenTc holotoxin prepore and pore reveal the evolutionary basis for chitinase incorporation into ABC toxins.Nature communications · 2025Article
- Genomic characterization ofMicrobial genomics · 2025Article
- Anthrax Toxin: A Pioneer of Targeted Protein Toxins.Toxins · 2025Review
- Injection of Affibodies by a Self-Organizing Bacterial Syringe to Interfere with Intracellular Signaling.Toxins · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tc toxins are pore-forming virulence factors of many pathogenic bacteria. Following pH-induced conformational changes, they perforate the target membrane like a syringe to translocate toxic enzymes into a cell. Although this complex transformation has been structurally well studied, the reaction pathway and the resulting temporal evolution have remained elusive. We used an integrated biophysical approach to monitor prepore-to-pore transition and found a reaction time of ~30 hours for a complete transition. We show two asynchronous general steps of the process, shell opening and channel ejection, with the overall reaction pathway being a slow multistep process involving three intermediates. Liposomes, an increasingly high pH, or receptors facilitate shell opening, which is directly correlated with an increased rate of the prepore-to-pore transition. Channel ejection is a near-instantaneous process which occurs with a transition time of <60 milliseconds. Understanding the mechanism of action of Tc toxins and unveiling modulators of the kinetics are key steps toward their application as biomedical devices or biopesticides.
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Registered trials
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