Distant relatives of a eukaryotic cell-specific toxin family evolved a complement-like mechanism to kill bacteria.

Autor: Abrahamsen HL; Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Sanford TC; Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Collamore CE; Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Johnstone BA; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia., Coyne MJ; Duchossois Family Institute and Department of Microbiology, University of Chicago, Chicago, IL, USA., García-Bayona L; Duchossois Family Institute and Department of Microbiology, University of Chicago, Chicago, IL, USA., Christie MP; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia., Evans JC; Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.; Wheeler Bio, Oklahoma City, OK, 73104, USA., Farrand AJ; Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.; Wheeler Bio, Oklahoma City, OK, 73104, USA., Flores K; Duchossois Family Institute and Department of Microbiology, University of Chicago, Chicago, IL, USA., Morton CJ; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia.; CSIRO Biomedical Manufacturing Program, Clayton, VIC, 3168, Australia., Parker MW; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia. mwp@unimelb.edu.au.; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3010, Australia. mwp@unimelb.edu.au.; Australian Cancer Research Foundation Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, VIC, 2065, Australia. mwp@unimelb.edu.au., Comstock LE; Duchossois Family Institute and Department of Microbiology, University of Chicago, Chicago, IL, USA. lecomstock@uchicago.edu., Tweten RK; Department of Microbiology & Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. rod-tweten@ouhsc.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 12; Vol. 15 (1), pp. 5028. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1038/s41467-024-49103-5
Abstrakt: Cholesterol-dependent cytolysins (CDCs) comprise a large family of pore-forming toxins produced by Gram-positive bacteria, which are used to attack eukaryotic cells. Here, we functionally characterize a family of 2-component CDC-like (CDCL) toxins produced by the Gram-negative Bacteroidota that form pores by a mechanism only described for the mammalian complement membrane attack complex (MAC). We further show that the Bacteroides CDCLs are not eukaryotic cell toxins like the CDCs, but instead bind to and are proteolytically activated on the surface of closely related species, resulting in pore formation and cell death. The CDCL-producing Bacteroides is protected from the effects of its own CDCL by the presence of a surface lipoprotein that blocks CDCL pore formation. These studies suggest a prevalent mode of bacterial antagonism by a family of two-component CDCLs that function like mammalian MAC and that are wide-spread in the gut microbiota of diverse human populations.
(© 2024. The Author(s).)
Databáze: MEDLINE
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