<i>Vibrio</i> MARTX toxin binding of biantennary N-glycans at host cell surfaces.

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 surfaces have remained elusive. Here, we map a surface interaction domain of a MARTX toxin from the highly lethal foodborne pathogen <i>Vibrio vulnificus</i>. This domain corresponds to a 273-amino acid sequence with predicted symmetrical immunoglobulin-like folds. We demonstrate that this domain binds internal <i>N</i>-acetylglucosamine on complex biantennary N-glycans with select preference for L1CAM and other N-glycoproteins with multiple N-glycans on host cell surfaces. This domain is also essential for <i>V. vulnificus</i> pathogenesis during intestinal infection. The identification of a highly conserved motif universally present as part of all N-glycans correlates with the <i>V. vulnificus</i> MARTX toxin having broad specificity and targeting nearly all cell types.