Abstract
Actin crosslinking toxins produced by Gram-negative bacteria represent a small but unique class of bacterial protein toxins. For each of these toxins, a discrete actin crosslinking domain (ACD) that is a distant member of the ATP-dependent glutamine synthetase family of protein ligases is translocated to the eukaryotic cell cytosol. This domain then incorporates a glutamate-lysine crosslink between actin monomers, resulting in destruction of the actin cytoskeleton. Recent studies argue that the function of these toxins during infection is not destruction of epithelial layers, but rather may specifically target phagocytic cells to promote survival of bacteria after the onset of innate immune defenses. This review will summarize key experiments performed over the past 10 years to reveal the function of these toxins.
Highlights
Actin crosslinking toxins produced by Gram-negative bacteria represent a small but unique class of bacterial protein toxins
Studies over the past ten years have been directed toward characterizing a distinct mechanism to disrupt actin filament assembly by covalently crosslinking actin monomers
An actin crosslinking toxin was first discovered in current pandemic strains of the human diarrheal pathogen Vibrio cholerae [6]
Summary
Many toxins have been characterized that disrupt the eukaryotic actin cytoskeleton. These include fungal and marine small molecule toxins that bind to actin to prevent actin polymerization [1,2]. Toxins have been identified that covalently modify actin itself, for example by the addition of an ADP-ribosyl group that prevents its incorporation into F-actin [4,5]. Studies over the past ten years have been directed toward characterizing a distinct mechanism to disrupt actin filament assembly by covalently crosslinking actin monomers. The crosslinks can be Toxins 2009, 1 introduced repetitively to form long chains of dysfunctional actin that cannot be incorporated into. F-actin filaments, resulting in irreversible destruction of the host cell cytoskeleton [6]
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