Project-ID: LS16-016
Project start: 01. November 2017
Project end: will follow
Runtime: 36 months / finished
Funding amount: € 249.000,00

Brief summary:

Candida cells are common human commensals found on the skin and genitourinary tract. They cause mucosal infections which may progress to systemic candidosis. Of all cases of vulvo-vaginal candidosis (VVC) C. albicans and C. glabrata species occur in 90% and 8%, respectively. In the vaginal tract Candida cells compete with the commensal bacterial microflora. In healthy individuals bacteria and fungi co-exist in equilibrium. Treatment with antifungals aims at restoring the microbial balance. Here we propose to address current VVC treatment along three lines 1) to investigate the interactions that occur between Candida spp. and three abundant Lactobacillus species found in the vaginal tract to support the establishment of equilibrium; 2) to analyse local (eastern Austrian) candida strains for their genetic traits; and 3) to evaluate the efficacy of common probiotics and 4) find novel substances able to fight fungi and promote bacteria. The consortium combines clinical resources, molecular biology of Candida, cell culture, and robotic screening.
Lactobacillus spp. restrict the progress of Candida in the vaginal tract by producing lactic and acetic acid and also by influencing in an undefined manner the nutrient availability, adherence to vaginal epithelium, biofilm formation, quorum sensing and stress resistance. The environmental and genetic factors triggering microbial imbalance in the vaginal tract constitute a complex host-microbe interaction system. We will address the Candida-Lactobacillus interaction in vitro in combinatorial co-culture on reconstituted human epithelium model system. We will especially focus on C. glabrata since it is harder to treat and much less explored compared to C. albicans. We will attempt to identify C. glabrata genetics and physiological responses involved in colonization of the vaginal tract. The physiological aspect covers the Candida-Lactobacillus interference on gene expression, adherence and biofilm formation properties. Genetic analysis will exploit and characterize lower Austria region clinical C. glabrata isolates. Furthermore, compounds will be screened in high throughput for their ability to foster the presence of different Lactobacillus strains and suppress the growth of Candida.
We expect the identified novel targets to be useful for antifungal strategies against Candida to favour benign commensal populations. A considerable industry is selling probiotics for this purpose however with only partly documented efficacy. The projected work will seek novel alternative compounds to improve treatments in the future.

Keywords:
mycology, biochemistry,, genetics