A novel path to kill pathogens
A dangerous, increasingly common infection caused by an opportunistic and sometimes deadly bacterium keeps Julian Hurdle awake at night plotting ways to defeat it.
The biology assistant professor is researching the viability of a new treatment for those with Clostridium difficile, also called C. difficile or C. diff, which causes severe diarrhea and intestinal diseases. It strikes the elderly, cancer patients, and others with compromised immune systems. Of the 500,000 cases in the United States each year, about 15,000-20,000 are fatal.
“C. difficile infections have become more widespread and difficult to treat over the past 10 years, with high rates of relapse,” Dr. Hurdle says. “With only a few drugs available, there is a great clinical need and a market opportunity in developing treatments for C. difficile infections.”
Hurdle is principal investigator of a five-year, $1.9 million grant awarded by the National Institutes of Health’s National Center for Complementary & Alternative Medicine. His co-investigator is Richard Lee, a faculty member at St. Jude Children’s Research Hospital in Memphis, Tenn.
“Julian is an outstanding talent. He’s brilliant and we’ve always worked very well together,” Dr. Lee says. “This study is very important because this pathogen is very dangerous for older people and has a tendency to persist.”
Hurdle and Lee have collaborated for more than four years, since the days when Lee was Hurdle’s postdoctoral mentor and Hurdle ran Lee’s microbiology lab at the University of Tennessee Health Science Center in Memphis. Their current work examines the effects of reutericyclin compounds on C. difficile. Reutericyclin is an antimicrobial compound produced naturally by a probiotic organism called Lactobacillus reuteri. The researchers have produced synthetic forms of reutericyclin in the lab with improved antibacterial properties.
They’re working on boosting the effectiveness of their compounds and exploring how they work against the infection. They believe reutericyclin is unique because it attacks the membrane of the C. difficile cells, killing them by affecting multiple cellular processes the bacteria need to survive. Lee’s lab produces the compounds and sends them to Hurdle’s lab for testing.
“We’re making good progress,” Hurdle says. “For the compounds that don’t work, we can find out why they didn’t work and then make changes in the chemistry to improve them.”
C. diff infections most commonly affect older adults in hospitals or long-term care facilities and typically occur after use of broad-spectrum antibiotic medications. These antibiotics often have the adverse effect of killing helpful micro-organisms that occur naturally in the intestines, leaving the patient vulnerable to C. diff. Spores of the bacterium can then germinate, producing cells that rapidly release toxins that can cause severe diarrhea and colitis (the latter can lead to life-threatening inflammation of the colon). Many people affected already have weakened immune systems.
Hurdle’s UT Arlington team includes postdoctoral fellow Wendy Wu, doctoral student Zahidul Alam, and technician Briony Foster. They’re focusing on the stationary phase of C. diff development, when the bacterium releases spores. In previous research, Hurdle and Lee found that reutericyclin rapidly kills the infection in the stationary phase, something antibiotics currently used to treat the ailment—Vancomycin and Metronidazole—haven’t achieved. Another major component to the research is finding a way to stop C. diff’s ability to recur after initial treatment.
“The standard antibiotics currently being used don’t prevent C. diff spores from re-forming after relieving the initial infection,” Hurdle says. “That’s one of the primary challenges we’re trying to overcome. Hopefully we’ll find a compound that can stand up well and help us get the upper hand. If we can, it could help a lot of people, and that’s very exciting.”