ArticleNature communications2021
Toxin import through the antibiotic efflux channel TolC.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Bacteriocin biophysics: From protein-protein interaction models to navigators of the bacterial cell envelope.The Journal of biological chemistry · 2026Article
- TheFrontiers in medicine · 2026Article
- A new strategy for the diagnosis of tuberculosis based on secreted antigens: evaluation of the efficacy of alveolar lavage ESAT-6 and CFP-10 tests.European journal of medical research · 2025Article
- RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance.Biophysical reviews · 2025Review
- Substrate Uptake by TonB-Dependent Outer Membrane Transporters.Molecular microbiology · 2024Review
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.ACS infectious diseases · 2024Review
- Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures.Physical biology · 2024Article
- Gating of β-Barrel Protein Pores, Porins, and Channels: An Old Problem with New Facets.International journal of molecular sciences · 2023Review
- Mass spectrometry of intact membrane proteins: shifting towards a more native-like context.Essays in biochemistry · 2023Review
- A coevolution experiment betweenMicrobiology (Reading, England) · 2023Article
- The role of bacterial transport systems in the removal of host antimicrobial peptides in Gram-negative bacteria.FEMS microbiology reviews · 2022Review
- Colicin E1 opens its hinge to plug TolC.eLife · 2022Article
- Insights into coastal microbial antibiotic resistome through a meta-transcriptomic approach in Yucatan.Frontiers in microbiology · 2022Article
- Nutrient Gradients Mediate Complex Colony-Level Antibiotic Responses in Structured Microbial Populations.Frontiers in microbiology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Bacteria often secrete diffusible protein toxins (bacteriocins) to kill bystander cells during interbacterial competition. Here, we use biochemical, biophysical and structural analyses to show how a bacteriocin exploits TolC, a major outer-membrane antibiotic efflux channel in Gram-negative bacteria, to transport itself across the outer membrane of target cells. Klebicin C (KlebC), a rRNase toxin produced by Klebsiella pneumoniae, binds TolC of a related species (K. quasipneumoniae) with high affinity through an N-terminal, elongated helical hairpin domain common amongst bacteriocins. The KlebC helical hairpin opens like a switchblade to bind TolC. A cryo-EM structure of this partially translocated state, at 3.1 Å resolution, reveals that KlebC associates along the length of the TolC channel. Thereafter, the unstructured N-terminus of KlebC protrudes beyond the TolC iris, presenting a TonB-box sequence to the periplasm. Association with proton-motive force-linked TonB in the inner membrane drives toxin import through the channel. Finally, we demonstrate that KlebC binding to TolC blocks drug efflux from bacteria. Our results indicate that TolC, in addition to its known role in antibiotic export, can function as a protein import channel for bacteriocins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.