Researchers at The University of Texas Health Science Center (UTHealth) School of Public Health have identified the location of genes that control production of toxins that harm people infected by Clostridium difficile bacteria. The gene location, agr1, forms part of a signaling communication system that produces a small peptide that, in turn, tells the rest of the Clostridium difficile population to turn on their toxin genes. The study was published in mBio here.

[Photo: Dr. Charles Darkoh]

Clostridium difficile causes severe diarrheal diseases by producing toxins, the most virulent of which are known as Toxin A and Toxin B. The C. difficile bacteria resist most of the available antibiotics.

Study leader and molecular microbiologist Dr. Charles Darkoh, assistant professor in the department of epidemiology, human genetics and environmental sciences at UTHealth School of Public Health, has been studying this bacterium since 2007. He said researchers did not previously know the role of agr1 in C. difficile infections. His group’s findings, which combined genetic analysis of C. difficile with animal models, suggest a new way to treat the disease. The new treatment involves jamming this signaling communication system and stopping toxin production.

“It has become important to develop a non-antibiotic therapy for this life-threatening infection,” said Dr. Darkoh. “We have uncovered a pathway that we and other researchers can target to develop a non-antibiotic therapy for C. difficile infections.”

1. difficile ordinarily live in the intestines – of humans, as well as animals – as one of many non-harmful bacterial species. However, when a person undergoes long-term antibiotic therapy, the medicine can wipe out helpful bacterial species that keep C. difficile in check. As a result, the bacteria flourish, producing toxins and causing problems. Some people experience only mild symptoms. For others, it’s fatal. The infection causes a variety of dangerous diarrheal diseases and toxic megacolon.

People in hospitals and long-term care facilities face the highest risk of infection. According to the Centers for Disease Control and Prevention, C. difficile infections caused nearly 500,000 infections and killed about 29,000 people in 2011.

1. difficile infections are notoriously difficult to treat and infections have increased in severity and number since the beginning of the 21st century, especially among older patients. Doctors typically prescribe one of three antibiotics, but patients can become resistant to those treatments. Infections recur in as many as 25 to 30 percent of cases. C. difficile infection is a major public health problem and finding a non-antibiotic method of treating C. difficile infections is critical to public health, according to Darkoh.

“Bacteria always find a way to survive when they are under pressure to die,” said Dr. Darkoh.

He is currently developing an oral drug that wouldn’t kill the bacteria. Instead, it would inactivate the toxins and cripple the toxin-making machinery of C. difficile by targeting the pathways regulated by agr1.

Adapted from a press release by mBio. Read the story here.