Charles Darkoh, Ph.D., a researcher at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, was recently awarded a five-year, $1.9 million R01 grant by the National Institutes of Health (NIH) to develop a non-antibiotic treatment for Clostridium difficile (C. diff) infections.
C. diff, a bacterium that causes diarrhea and inflammation of the colon, is one of the most common causes of hospital-acquired and antibiotic-associated diarrhea in the United States. Treatment of the infection costs the health care system at least $1 billion annually, according to the Centers for Disease Control and Prevention.
One of the major risk factors for C. diff infections is indiscriminate antibiotic use, which kills the good bacteria that protect the gut from bad bacteria. As a multidrug-resistant pathogen, C. diff temporarily takes over the colon after the good bacteria have been wiped out by antibiotic treatment.
According to Darkoh, C. diff causes illness by releasing two potent toxins into the gut- toxin A and toxin B. The bacterium also produces spores that can persist in a room or in the environment for weeks or months. Following infection, the spores germinate into the form that produces the toxins.
The three antibiotics that are used to treat C. diff are unable to permanently eliminate the spores. The spores can stay in the gut until the treatment ends and then emerge again after several weeks, creating recurrent infections.
"If we can prevent C. diff from making the toxins and/or make the toxins inactive in the gut without killing the good bacteria, that would be a better treatment option," said Darkoh, the principal investigator and assistant professor in the Department of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health.
The majority of the antibiotics currently used for treatment work by either killing bacteria or preventing their growth, but Darkoh says "C. diff has found multiple ways to survive several antibiotics." By preventing C. diff from releasing toxins and making the existing toxins inactive, the treatment would give good bacteria time to repopulate the gut and allow the immune system to naturally clear the infection.
Illness from C. diff commonly affects the elderly and immunocompromised. It is mostly transmitted in hospitals and nursing homes. "If you go to the hospital and one patient has C. diff, the spores are all over the room. If the doctor treats that patient and then goes to another patient, it can be easily transmitted," said Darkoh, who is also a faculty member at the Center for Infectious Diseases at the School of Public Health.
Darkoh's laboratory has identified potent novel compounds that prevent production of the C. diff toxins and also inactivate the toxins. During the pre-clinical study, Darkoh will identify the target and mechanism of inhibition of the compounds, evaluate the compounds on different strains of C. diff and examine the efficacy of a cocktail of these compounds that would work as a combination therapy to prevent illness from C. diff.
Researchers at the Center for Infectious Diseases at the School of Public Health have been involved in many important clinical trials of C. diff treatment and prevention, including fecal microbial transplants.
"C. diff infection is a growing problem in the United States. The research proposed by Dr. Darkoh is an innovative first step to quickly identify novel treatments for this condition by focusing on already-approved drugs and redirecting them toward this new and important purpose," said Eric Boerwinkle, Ph.D., professor and chair of the Department of Epidemiology, Human Genetics and Environmental Sciences at the School of Public Health.
University of Texas Health Science Center at Houston