ArticleEmerging microbes & infections2018
Cytotoxic activity of Kingella kingae RtxA toxin depends on post-translational acylation of lysine residues and cholesterol binding.
Article in Emerging microbes & infections, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Calcium-loaded acylated segment controls membrane penetration capacity of repeats-in-toxin cytolysins.The Journal of biological chemistry · 2026Article
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- Toxin-triggered liposomes for the controlled release of antibiotics to treat infections associated with the gram-negative bacterium, Aggregatibacter actinomycetemcomitans.Colloids and surfaces. B, Biointerfaces · 2024Article
- Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity.International journal of molecular sciences · 2024Review
- Infective Endocarditis Due toMicroorganisms · 2024Review
- Heterologously secreted MbxA from Moraxella bovis induces a membrane blebbing response of the human host cell.Scientific reports · 2022Article
- Four Cholesterol-Recognition Motifs in the Pore-Forming and Translocation Domains of Adenylate Cyclase Toxin Are Essential for Invasion of Eukaryotic Cells and Lysis of Erythrocytes.International journal of molecular sciences · 2022Article
- Review
- Review
- Pathogenic determinants ofFrontiers in pediatrics · 2022Review
- Cholesterol stimulates the lytic activity of Adenylate Cyclase Toxin on lipid membranes by promoting toxin oligomerization and formation of pores with a greater effective size.The FEBS journal · 2021Article
- Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins.Scientific reports · 2021Article
- Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function.Frontiers in cell and developmental biology · 2021Review
- Proinflammatory Microenvironment DuringFrontiers in immunology · 2021Article
- Binding ofInternational journal of molecular sciences · 2020Article
- Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins.The Journal of biological chemistry · 2020Article
- Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti-toxin therapeutics.Molecular oral microbiology · 2020Review
- Article
- Review
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Kingella kingae is a member of the commensal oropharyngeal flora of young children. Improvements in detection methods have led to the recognition of K. kingae as an emerging pathogen that frequently causes osteoarticular infections in children and a severe form of infective endocarditis in children and adults. Kingella kingae secretes a membrane-damaging RTX (Repeat in ToXin) toxin, RtxA, which is implicated in the development of clinical infections. However, the mechanism by which RtxA recognizes and kills host cells is largely unexplored. To facilitate structure-function studies of RtxA, we have developed a procedure for the overproduction and purification of milligram amounts of biologically active recombinant RtxA. Mass spectrometry analysis revealed the activation of RtxA by post-translational fatty acyl modification on the lysine residues 558 and/or 689 by the fatty-acyltransferase RtxC. Acylated RtxA was toxic to various human cells in a calcium-dependent manner and possessed pore-forming activity in planar lipid bilayers. Using various biochemical and biophysical approaches, we demonstrated that cholesterol facilitates the interaction of RtxA with artificial and cell membranes. The results of analyses using RtxA mutant variants suggested that the interaction between the toxin and cholesterol occurs via two cholesterol recognition/interaction amino acid consensus motifs located in the C-terminal portion of the pore-forming domain of the toxin. Based on our observations, we conclude that the cytotoxic activity of RtxA depends on post-translational acylation of the K558 and/or K689 residues and on the toxin binding to cholesterol in the membrane.
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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.