Bacterial toxin and effector glycosyltransferases

Yury Belyi1, Klaus Aktories

  • 1Gamaleya Research Institute, Moscow 123098, Russia.

Insights

Bacterial glucosylating cytotoxins from Clostridium and Legionella modify host proteins. These toxins, targeting Rho/Ras proteins and elongation factor eEF1A, disrupt cellular functions and cause disease.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Toxicology

Background:

  • Clostridial glucosylating cytotoxins (e.g., C. difficile toxins A/B, C. novyi alpha-toxin, C. sordellii lethal toxin) are key virulence factors in human diseases.
  • These toxins target Rho/Ras proteins, essential molecular switches, by mono-O-glucosylation at a threonine residue, impairing their function.

Purpose of the Study:

  • To discuss recent findings on the structures, functions, and biological roles of bacterial toxin glucosyltransferases.
  • To highlight the newly identified glucosyltransferases from Legionella pneumophila and their distinct targets.

Main Methods:

  • Comparative analysis of toxin structures and enzymatic mechanisms.
  • Functional studies on host-pathogen interactions.
  • Biochemical assays to characterize glycosylation activities.

Main Results:

  • Clostridial toxins glucosylate Rho/Ras proteins, disrupting actin cytoskeleton regulation.
  • Legionella glucosyltransferases modify elongation factor eEF1A at a serine residue.
  • This modification by Legionella enzymes inhibits host cell protein synthesis.

Conclusions:

  • Bacterial glucosylating toxins represent a significant class of virulence factors with diverse targets and mechanisms.
  • Understanding these toxins' structures and functions is crucial for developing therapeutic strategies against bacterial infections.

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