The world now understands all too well the peril of coronaviruses. Yet, microbiologists and healthcare professionals also know the dangers of another destructive microbe. Clostridium difficile is a bacterium that causes infection in hospitals or outside clinics in patients after a round of powerful antibiotics. (Antibiotics can wipe out not only an offending bacterium but also the body’s beneficial, gut-inhabiting microbiome, leaving a person vulnerable to opportunistic infections).
C. diff, as scientists call the microbe, can cause symptoms ranging from dehydration to diarrhea to life-threatening inflammation of the colon. Scarily, an infected person can be treated, show no symptoms, but still transmit the infection; the bacteria can live on or in a person for months.
You may ask why we are writing about this specific microbe while the planet is reeling from COVID-19.
As healthcare workers well know, illness outside of SARS Cov-2 still is happening. In fact, many people are having a more challenging time accessing treatments for any sickness in this time of social distancing and quarantines.
C. diff is the single most common cause of healthcare-associated infections in the US, afflicting more than 11 million Americans and causing 15 thousand deaths each year. There are no effective or reliable treatments, as C. diff can take refuge in bunker-like spores that are able to withstand an arsenal of intravenous antibiotics.
To get in and take out the microbes, IPI scientists are working hard on a project to target C. diff.
Our team starts with the knowledge that two exotoxins mediate C. diff’s damage: TcdA and TcdB. Upon infection, the microbe secretes both into the intestinal mucosa. There, they immediately alter cells, dismantling their cytoskeletons. This leads to the accumulation of fibrin (a protein involved in blood clots), mucin (the basis of mucous), and dead cells to form a layer of debris in the colon that launches a destructive inflammatory response. Therefore, neutralizing the toxins would, in essence, block bacterial action and provide a much-needed therapy.
The Food and Drug Administration has approved a neutralizing antibody. However, healthcare practitioners must administer it intravenously because antibodies, in general, are not durable enough for oral administration on route to the gut. IPI scientists are in hot pursuit of a neutralizing agent, to be taken in oral form, that is tough enough to withstand the acid and digestive enzymes of the intestinal tract.
Stay tuned for more on IPI’s project.