A Starting Point for Treating a Challenging Infection
By LIDA TUNESI
Infections from Clostridium difficile bacterium, or C. diff, started to become a serious problem in the U.S. in the 2000s. Severe cases can lead to serious abdominal pain and kidney failure and are notoriously difficult to treat. The U.S. sees 500,000 cases of C. diff infections per year, 13,000 of which are fatal.
Now, a study published in the journal PNAS could pave the way for new C. diff drugs. The authors, including researchers from the Advanced Science Research Center at The Graduate Center, CUNY, and The City College of New York, deduced the structure of one of the toxins the bacterium produces, giving insight into how to tackle it.
While C. diff can be found in the soil, air, and water around us, most people get it from a health care facility. Bugs spread easily around hospitals and care facilities, and many of the occupants are already susceptible to infection. Certain antibiotics can also be risk factors for C. diff if they kill off too much of the “good” bacteria that normally inhabit your gut, thus making room for C. diff. Some strains of the bacterium are resistant to treatment, and in some patients the infection can recur.
C. diff bacterium produce several types of toxins. Some of the most serious strains of C. diff release what scientists simply call the C. difficile toxin. It has two components, CDTa and CDTb. CDTb binds to cells in the body and helps sneak CDTa inside them. In the new study, the researchers used a gamut of imaging methods to zoom in on CDTb and create an atom-by-atom picture of its structure.
From the structure, the researchers garnered knowledge specifically about two receptor-binding domains that could facilitate drug discovery. Knowing what CDTb looks like could also give clues as to how it works, giving scientists another edge in developing therapeutics.
“These details provide a critical and extremely useful starting point for designing drugs that can prevent C. diff infection,” said Professor Amédée des Georges of the CUNY ASRC and CCNY, an author on the study.