Tilivalline
Tilivalline is a pyrroloquinoline alkaloid produced by certain strains of the bacterium Klebsiella oxytoca. It is known for its role in causing antibiotic-associated hemorrhagic colitis, a condition characterized by inflammation and bleeding of the colon.
Production and Biosynthesis
Tilivalline is synthesized by Klebsiella oxytoca through a complex biosynthetic pathway. The production of tilivalline involves several enzymatic steps, starting from the precursor molecule tryptophan. The biosynthesis pathway includes the formation of intermediate compounds, which are subsequently modified to produce the final tilivalline structure.
Mechanism of Action
Tilivalline exerts its toxic effects by interfering with the epithelial cells lining the colon. It disrupts the integrity of the epithelial barrier, leading to increased permeability and inflammation. This disruption is a key factor in the development of hemorrhagic colitis.
Clinical Significance
The presence of tilivalline-producing Klebsiella oxytoca in the gut microbiota is associated with antibiotic-associated hemorrhagic colitis. This condition typically occurs after the administration of certain antibiotics, which disrupt the normal gut flora and allow the overgrowth of Klebsiella oxytoca. Symptoms of hemorrhagic colitis include abdominal pain, diarrhea, and bloody stools.
Diagnosis and Treatment
Diagnosis of tilivalline-associated hemorrhagic colitis involves identifying the presence of Klebsiella oxytoca in stool samples and detecting the production of tilivalline. Treatment typically involves discontinuing the offending antibiotic and providing supportive care. In some cases, alternative antibiotics may be used to target Klebsiella oxytoca.
Research and Future Directions
Ongoing research aims to better understand the biosynthesis of tilivalline and its role in disease. There is also interest in developing therapeutic strategies to prevent or mitigate the effects of tilivalline on the colon.
Related Pages
- Klebsiella oxytoca
- Pyrroloquinoline alkaloid
- Hemorrhagic colitis
- Antibiotic-associated colitis
- Gut microbiota
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Contributors: Prab R. Tumpati, MD