Type 4 secretion system in Clostridioides difficile: Structural features and its role as a pathogenicity factor

Abstract

Clostridioides difficile is a gram-positive microorganism causing damage to the human intestinal wall, clinically manifesting as antibiotic-associated diarrhea and pseudomembranous colitis. C. difficile infection remains a serious problem; the increasing frequency of nosocomial outbreaks and the emergence of community-acquired forms heighten the need for new prevention and treatment methods. The pathogenesis of C. difficile infection is associated with the toxins produced by bacteria and a large group of proteins promoting the replication of the pathogen in host tissues and its spread in the human population. Recent studies show that mobile genetic elements play a key role in the high virulence of C. difficile. Type 4 secretion systems (T4SS) are significant components of these elements; their impressive diversity among gram-positive microorganisms in general and in C. difficile, in particular, implies their high evolutionary and, consequently, medical significance. Further studies of the T4SS composition and structure will provide a deeper insight into mechanisms underlying the development of respective infections and will help outline pathogenically grounded approaches to prevention and treatment of diseases caused by C. difficile. On the other hand, the key components of the secretion machinery of the pathogen can be used in bioinformatic analysis and for searching new adaptive clusters in the genome of highly virulent strains.