ArticleInfection and immunity2007
Mannheimia haemolytica leukotoxin binds to lipid rafts in bovine lymphoblastoid cells and is internalized in a dynamin-2- and clathrin-dependent manner.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function.Frontiers in cell and developmental biology · 2021Review
- Article
- Review
- Aggregatibacter actinomycetemcomitans leukotoxin causes activation of lymphocyte function-associated antigen 1.Cellular microbiology · 2019Article
- Membrane localization of the Repeats-in-Toxin (RTX) Leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans.PloS one · 2018Article
- Inhibition of Bacterial Toxin Activity by the Nuclear Stain, DRAQ5™.The Journal of membrane biology · 2016Article
- Inhibition of LtxA toxicity by blocking cholesterol binding with peptides.Molecular oral microbiology · 2016Article
- Aggregatibacter actinomycetemcomitans leukotoxin utilizes a cholesterol recognition/amino acid consensus site for membrane association.The Journal of biological chemistry · 2013Article
- Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity.PloS one · 2011Article
- Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap formation by bovine neutrophils.Infection and immunity · 2010Article
- Selective translocation of the Bordetella pertussis adenylate cyclase toxin across the basolateral membranes of polarized epithelial cells.The Journal of biological chemistry · 2010Article
- Brief heat treatment increases cytotoxicity of Mannheimia haemolytica leukotoxin in an LFA-1 independent manner.Microbial pathogenesis · 2009Article
- Dynamin-2-dependent targeting of mannheimia haemolytica leukotoxin to mitochondrial cyclophilin D in bovine lymphoblastoid cells.Infection and immunity · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mannheimia haemolytica is the principal bacterial pathogen of the bovine respiratory disease complex. Its most important virulence factor is a leukotoxin (LKT), which is a member of the RTX family of exotoxins produced by many gram-negative bacteria. Previous studies demonstrated that LKT binds to the beta(2)-integrin LFA-1 (CD11a/CD18) on bovine leukocytes, resulting in cell death. In this study, we demonstrated that depletion of lipid rafts significantly decreases LKT-induced bovine lymphoblastoid cell (BL-3) death. After binding to BL-3 cells, some of the LKT relocated to lipid rafts in an LFA-1-independent manner. We hypothesized that after binding to LFA-1 on BL-3 cells, LKT moves to lipid rafts and clathrin-coated pits via a dynamic process that results in LKT internalization and cytotoxicity. Knocking down dynamin-2 by small interfering RNA reduced both LKT internalization and cytotoxicity. Similarly, expression of dominant negative Eps15 protein expression, which is required for clathrin coat formation, reduced LKT internalization and LKT-mediated cytotoxicity to BL-3 cells. Finally, we demonstrated that inhibiting actin polymerization reduced both LKT internalization and LKT-mediated cytotoxicity. These results suggest that both lipid rafts and clathrin-mediated mechanisms are important for LKT internalization and cytotoxicity in BL-3 cells and illustrate the complex nature of LKT internalization by the cytoskeletal network.
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