This is a story about a fungus—the cause of some serious infections in hospitalized patients—and a group of microbiologists with McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth) who want to develop a new antifungal drug.
Two of the most problematic causes of infections are Enterococcus faecalis, a bacterium, and Candida albicans, a fungus, often found together in the gastrointestinal region. These microbes can also co-habitate in the mouth; some studies have found evidence of both in materials extracted from infected root canals.
The presence of these two microbes in the same parts of the body led Michael Lorenz, Ph.D., a professor of microbiology and molecular genetics at UTHealth, and his colleague, Danielle Garsin, Ph.D., associate professor of microbiology and molecular genetics, to wonder how the organisms might affect one another.
When the researchers put the two organisms together, they noticed something interesting.
“We thought the two together would make infections worse,” Lorenz said. “What ended up happening was unexpected and fascinating: Enterococcus was actually returning Candida to a benign state.”
Doctoral student Carrie Graham deduced that a protein made by the bacterium, EntV, was blocking the fungus’ biofilm development. The interaction was inhibiting the Candida’s virulence, but not harming it. In fact, it was a completely new type of activity for this protein.
Using this newfound knowledge, the researchers wondered if this EntV protein would be effective against a Candida infection, in this case oral thrush—a yeast infection of the mouth and throat that affects millions, particularly babies, seniors and people with weakened immune systems.
In a mouse model, the researchers found that the animals treated with the antimicrobial protein had fewer symptoms—including a reduction in the creamy, white lesions associated with oral thrush—than those who were not treated with the antimicrobial protein. Their results were reported in the April issue of Proceedings of the National Academy of Sciences of the United States of America.
“These findings demonstrate that EntV has potential as an antifungal agent that targets virulence rather than viability,” the researchers wrote in their study.
The next steps are for Garsin’s lab to determine how EntV is produced in Enterococcus, and Lorenz’s lab to determine how EntV makes Candida less infectious. The researchers are also trying to determine how the protein could be used in a clinical setting.
“It’s probably many years away,” Lorenz said, “in part because the protein needs to be modified to make it a suitable therapeutic.”
More testing will determine whether EntV is effective against strains of Candida resistant to traditional antifungals and whether it can be used with them to improve outcomes.
“The long-term goal is to develop a new antifungal drug that takes a different approach to treating oral thrush,” Garsin said.
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