Year: 2025
Type: article
Abstract: ABSTRACT Multifunctional Autoprocessing Repeats-in-Toxin (MARTX) toxins are a diverse effector delivery platform of many Gram-negative bacteria that infect mammals, insects, and aquatic animal hosts. The mechanisms by which these toxins recognize host cell receptors for translocation of toxic effectors into the cell have remained elusive. Here, we map the first surface receptor-binding domain of a MARTX toxin from the highly lethal foodborne pathogen Vibrio vulnificus . This domain corresponds to a 273-amino acid sequence with predicted symmetrical immunoglobulin-like folds. We demonstrate that this domain binds internal N -acetylglucosamine on complex biantennary N-glycans with select preference for L1CAM and other N-glycoproteins with multiple N-glycans on host cell surfaces. This receptor binding domain is essential for V. vulnificus pathogenesis during intestinal infection. The identification of a highly conserved motif universally present as part of all N-glycans correlates with the V. vulnificus MARTX toxin boasting broad specificity and targeting nearly all cell types.
Source: Science Advances
Institutions: Northwestern University, University of Copenhagen
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: Northwestern University, National Research Foundation, Danmarks Grundforskningsfond, Lundbeckfonden, Novo Nordisk, Faculty of Health and Medical Sciences, University of Western Australia, H. Lundbeck A/S, Robert H. Lurie Comprehensive Cancer Center, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1164661550, G1954868685, G2375638104, Determine host surface interactions of MARTX toxin of foodborne Vibrio vulnificus, G317886719, Vibrio vulnificus toxin-receptor interactions, Molecular Biophysics Training Program at Northwestern University, G6350171285, The Robert H. Lurie Comprehensive Cancer Center, Vibrio MARTX toxin effectors in signaling and pathogenesis
OpenAlex ID: W4409284925