"Our aim was to try to understand what microorganisms live in our mouths. A disturbed equilibrium of these microorganisms can lead to disease," said the study''s senior author Mahmoud A. Ghannoum, PhD, EMBA, professor of dermatology and pathology at the School of Medicine and director of the Center for Medical Mycology at UH Case Medical Center.
The study involved testing the mouths of 24 patients from UH Case Medical Center - 12 HIV infected and 12 not infected with HIV. HIV-infected patients were selected for comparison in the study because thrush is a common occurrence for them. The oral cavity was tested for fungi and bacteria using pyrosequencing, a method that uses DNA analysis, which is more powerful with greater specificity than conventional, culture-based approaches.
"When we looked at the data, we found to our surprise that bacteria did not change much between HIV-infected patients and those who were not," Ghannoum said. "However, what changed significantly between the two groups was the composition of the fungal community. We found that when Candida
is present, Pichia
is not, and when Pichia
is present, Candida
is not - indicating Pichia
plays an important role in treating thrush."
From these observations, investigators conducted in vitro (test tube) experiments on Candida
. When they grew Candida
in the test tube in the presence of Pichia
, there was a striking reduction in Candida
growth. They also discovered that Pichia
secretes material, or a protein, that controls Candida
. This Pichia
-secreted material, referred to as supernatant, inhibits biofilm formation, germination and adherence in Candida
, factors that mark a microbe''s level of harmfulness.
Investigators then took their findings to the next level with experiments on three groups of Candida
-infected mice. One group of mice was treated with Pichia
supernatant. The next group was treated with nystatin, a topical treatment for thrush. Still another group received no treatment. The outcome? In the mouths of the Pichia
-treated mice, the level of Candida
was nearly eradicated, though traces remained. Even the nystatin-treated mice had far more Candida
present than the Pichia
-treated mice. Additionally, the physical symptoms, such as tongue appearance, improved in the Pichia
"One day, not only could this lead to topical treatment for thrush, but it could also lead to a formulation of therapeutics for systemic fungal infections in all immunocompromised patients," he said. "In addition to patients with HIV, this would also include very young patients and patients with cancer or diabetes."
As a next step this year, investigators will study Pichia
supernatant to identify its components that inhibit Candida
and other fungi.