Scientists have found that a dangerous bacterium capable of causing serious gut infections is triggered by excess calcium in its environment, but the triggering factor might also provide the solution.
Clostridium difficile is a bacterium that chiefly affects older patients living in nursing homes, or those who have been confined to a hospital environment for a long time. Research shows that people most at risk are those undergoing long-term broad-spectrum antibiotic treatments, which weaken the immune system and leave patients vulnerable to infectious diseases.
Spores of C. difficile are spread through feces, contaminating any objects or surfaces they come into contact with. The most common means of further transmission is through the hands of healthcare professionals, who unwittingly come into contact with contaminated items.
C. difficile infection can cause a wide array of bowel ailments, with the least serious being diarrhea and the most dangerous being colitis, or inflammation of the colon, which leads to death in some cases.
The bacterium forms
Calcium nourishes C. difficile
The research laboratories of the University of Michigan Medical School (U-M) in Ann Arbor, together with those of the United States Food and Drug Administration (FDA), have studied the conditions necessary for C. difficile to release its spores.
The teams were led by Travis Kochan and Philip Hanna, Ph.D., both from U-M, and Dr. Paul Carlson, Ph.D., from the FDA, and their results were recently published in the journal PLOS Pathogens.
It was discovered that excess calcium causes C. difficile to germinate. This finding sheds new light as to why senior, long-term hospital patients and nursing home residents are the most exposed to C. difficile infections.
The researchers explained that many of these patients are prescribed medication or supplements that release extra calcium into their systems. Many also have low vitamin D levels, or their system is unable to absorb calcium due to various ailments.
C. difficile is able to track down the excess calcium. This, as well as taurocholate - which is a sodium salt produced from cholesterol - allows the bacterium to germinate.
Previous research published in the Journal of Bacteriology argued that glycine, an amino acid, was a key germinant for C. difficile, alongside taurocholate. Now, it has become apparent that only calcium and taurocholate are necessary for germination to occur.
"Much of the [C. difficile] spore's own weight is made of calcium, but we've shown that calcium from the gut can work with bile salts to trigger the enzyme needed to activate the spore and start the germination process."
Philip Hanna, Ph.D.
The experiment used mice to study the interactions between the bacterium and calcium, but the researchers argue that this aspect does not diminish the importance of the discovery for human patients.
Kochan points out that the "growth medium" for C. difficile used in the laboratories contained calcium. Since this could impact the experiment, he chemically removed the calcium already existent in the medium. This resulted in germination no longer occurring, despite other C. difficile nutrients having been left in.
Following this observation, additional research undertaken in Dr. Carlson's laboratories at the FDA supported the discovery that calcium is crucial for the bacterium's germination.
C. difficile spores were mutated so that they could not interact with glycine. It was found that they could still germinate and contaminate the mice in the presence of calcium.
Furthermore, both mutated and unaltered bacteria were able to release their own reserve of calcium upon germination, providing more nutrients to perpetuate on. Researchers noted that this observation is consistent with the behavior of C. difficile in its natural gut environment.
"C. diff spores have specialized to germinate in the gut environment, especially in the environment of the small intestine, where calcium and the bile salt injection from the liver comes in," says Kochan.
The recent discovery could provide specialists with a strategy to fight the spread of C. difficile infections. They suggest that instead of reducing the levels of excess calcium in contaminated systems, even more calcium should be added.
The abundance of calcium could trigger all the inactive C. difficile spores, thus making them easier to suppress using antibiotics, the scientists say. This move could also interrupt the process of transmission and further contamination, if successful.
The study carried out by the U-M and FDA laboratories provides hope for a more targeted and efficient treatment of C. difficile infections, yet the scientists advise that current courses of action should remain in place until further research is completed.