On the Potential Significance of the Intrinsically Disordered Regions in the Clostridiodes difficile Toxins A and B

Abstract

Background: Clostridiodes (or Clostridium) difficile is a spore-forming, Gram-positive anaerobic bacterium that may cause symptoms ranging from diarrhea to pseudomembranous colitis. During the C. difficile infection (CDI), the two primary bacterial toxins, toxin A (TcdA) or toxin B (TcdB), disrupt host cell function mainly through the inactivation of small GTPases that regulate the actin cytoskeleton. Both toxins have complex structural organization containing several functional domains. Methods: Analytical bioinformatics tools are used to compare the extent of disorder within TcdA and TcdB proteins, and to see if the existence of structural disorder can be used to explain the difference in the functionality of these toxins. Results: This paper’s aim is to offer an overall review of the structural and functional differences between TcdA and TcdB. Conclusions: Results of our multifactorial bioinformatics analysis revealed that intrinsic disorder may play a role in the multifunctionality of C. difficile major toxins TcdA and TcdB, suggesting that intrinsic disorder may be related to their pathogenic mechanisms.