Work

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

Year: 2024

Type: article

Abstract: 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.

Source: Nature Communications

DOI: 10.1038/s41467-024-49103-5

Authors: Hunter L. Abrahamsen, Tristan C. Sanford, Casie E. Collamore, Bronte A. Johnstone, Michael J. Coyne, Leonor García-Bayona, Michelle P. Christie, Jordan C. Evans, Allison J. Farrand, Katia Flores, Craig J. Morton, Michael W. Parker, Laurie E. Comstock, Rodney K. Tweten

Institutions: University of Oklahoma Health Sciences Center, The University of Melbourne, University of Chicago, Commonwealth Scientific and Industrial Research Organisation, Australian Cancer Research Foundation, St Vincents Institute of Medical Research

Language: English

Topic: Clostridium difficile and Clostridium perfringens research

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,790

Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Australian Government, Australian Synchrotron, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: G1491271946, G1732273223, G2067509459, G2497749454, G3267130329, G445561835, G5530723066, Understanding cell signalling as a basis for new therapeutics, G658816337, Protective mechanisms of the gut Bacteroidales, Center for Interdisciplinary Study of Inflammatory Intestinal DIsorders (C-IID), Human gut Bacteroidales defense mechanisms against emerging antibacterial toxins, Probing short and long term consequences of Small and Large Bowel Microbiota Transplants on Host Physiology: Implications for the development of future live biotherapeutics

OpenAlex ID: W4399577166

FWCI: 3.461

Cites: 50

Cited by: 10

Related to: 10