Clostridium difficile (C.diff) moves in when antibiotics kill off other pathogens. Infection with this pathogen (CDI) causes most of the diarrheal outbreaks linked with antibiotic therapy. Unfortunately these are not quick bouts in the bathroom; CDI can cause dangerous weight loss and malnutrition in a short time period. Many thousands die even when treated.
C.diff is formidable, armored with spores, which survive in harsh environments for long periods of time. After initial treatment for C.diff—usually with more antibiotics—as many as 35% of patients develop the disease again. C.diff is a Gram-positive spore-forming anaerobe.
The devastating diarrhea and wasting inherent in recurrent infections have long frustrated clinicians. Throwing more and stronger antibiotics such as vancomycin at the culprit may work at times but for many that route seems to embolden C.diff. Scientists looked closer at this bacterium to see what made it so wily.
Clostridium difficile has a secret weapon
One unusual characteristic of C.diff among gut bacteria is its ability to produce the compound para-cresol (p-cresol) through fermentation of tyrosine. P-cresol has damaging effects on the natural protective gut bacteria. C.diff is one of the 18 bacterial species in the gut that produces p-cresol.
Lisa Dawson and colleagues from the London School of Hygiene and Tropical Medicine found that p-cresol gives C.diff an advantage over other intestinal bacteria. The research was published in journal PLOS Pathogens September 12, 2018: Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria
The scientists found that p-cresol selectively targets certain bacteria in the gut and disrupts their ability to grow. The compound effectively alters the composition and recovery of diversity in the intestinal microbiota. This was observed in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and fecal metabolite profiles,
As further evidence, strains of mutant C.diff that were unable to produce the p-cresol were less able to compete with other intestinal microbiota species in vitro thus less able to recolonize the intestine following initial infection.
Evidence that p-cresol production by C.diff provides it with a competitive survival advantage over other intestinal bacterial species
- Growth of helpful Gram-negative bacteria was targeted by p-cresol. Gram positive species were more tolerant.
- Exposure to p-cresol resulted in release of cellular phosphate, suggesting that it disrupts cell envelope integrity.
FYI: The cell envelope comprises the inner cell membrane and the cell wall of a bacterium. In gram-negative bacteria an outer membrane is also included. Watch video below for excellent explanation.
In conclusion the authors stated:
Our study provides new insights into the effects of p-cresol production on the healthy gut microbiota and how it contributes to C.diff survival and pathogenesis.
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