Understanding Clostridioides difficile Genetics

Clostridioides difficile (C difficile) is a bacterium found in human and animal intestinal tracts. When it gets on food, is present in antibiotics, etc, can harm the human body and cause diarrhea or fulminant colitis, which can lead to further issues like toxic megacolon or sepsis. Commonly, C difficile is transmitted orally. The flagellum also plays a key role in the transference of the infection and could be the key to creating new therapies. Understanding the genetic makeup of C difficile infection can lead to researchers creating more vaccinations and therapies to help prevent/manage the sickness.

C difficile has 2 types of strains: ON and OFF. The ON strain has genes that express in the early operon encoding of the flagellar hook, basal body, MS ring, motor, as well as other proteins. Bacteria that are the inverse of ON are OFF and show decreased toxin gene expression. Strain heterogeneity has proven itself to be a problem for researchers, as bacteria in the OFF phase have higher variability and impact the infection ability of the strain. Researchers also analyzed how the flagellar genes of C difficile bacteria would interact with heat, and they found that the genes encoding the hook, rod, and basal body were up-regulated.

Thousands of flagellin monomers make up flagellar filaments, and are made up of 4 domains: D0, D1, D2, and D3. D0 and D1 domains face inwards towards the filament core. D2 and D3 domains face outward, away from the core. There are also 2 different genetic organizations of the flagellar F2 glycosylation operon that are named the type A and type B systems. In the type A organization, there are 4 genes. These genes are a putative glycosyltransferase, a hypothetical open reading frame, and a second glycosyltransferase. In type B, there are 6 different genes. These genes are 2 glycosyltransferases, 2 putative uncharacterized proteins, a putative carbamoylphosphate synthetase, and a putative ornithine cyclodeaminase.

Toxin-based vaccines are not the answer to C difficile infection prevention. Researchers have found that something that does hold promise is the initiation of directed antibodies against molecules that are involved in the adhesion or colonization process. They have also found that the flagellar components of the bacteria, FLiA, FLiB, FLiC, and FliD are more promising as candidates for antibodies.

Worldwide, C difficile is the most common cause for nosocomial diarrhea. Researchers believe that flagellum expression and toxic gene expression play a big role in pathogenicity. If researchers can break down the mechanisms of flagellum synthesis during the process of gastrointestinal tract colonization, they will be able to understand the infection better and have a more effective vaccine for the sickness.

Reference

Marvaud JC, Bouttier S, Saunier J, Kansau I. Clostridioides difficile flagella. Int J Mol Sci. 2024;25(4):2202. doi:10.3390/ijms25042202