Beta-1,3 glucan in Candida albicans biofilm infection: Drug resistance and diagnosis.

摘要

Candida albicans, the most common human fungal pathogen, causes both superficial and deep fungal infections. A recently recognized virulence trait of C. albicans is the ability to grow as a biofilm composed of adherent cells encased in an extracellular matrix produced by the cells. Upon adapting to a biofilm lifestyle, Candida is capable of causing life-threatening infections by attaching to the surface of medical devices. Cells in this environment are phenotypically distinct, exhibiting up to 1000-fold increased drug resistance compared to non-biofilm cells. Because this extraordinary drug resistance is a major obstacle for treatment, Candida device-associated infections require prompt attention and device removal. However, there are no diagnostic tests for Candida biofilm infection.;We have developed and characterized an in vivo central venous catheter C. albicans biofilm model, as well as an in vitro biofilm model, which have been instrumental in our analysis of biofilm pathogenesis and drug resistance. Transcriptional analysis of venous catheter biofilm cells identified an abundance transcripts involved in carbohydrate metabolism. Therefore, we hypothesized that the extracellular matrix beta-1,3 glucan as a key component. Using a set of genetically modified strains, we linked expression of beta-1,3 glucan synthase gene FKS1 to the manufacture of extracellular glucan. This material is incorporated into an adhesive, carbohydrate-rich matrix critical for biofilm resistance to a variety of antifungal compounds, but is not needed for drug resistance during non-biofilm growth. The matrix glucan acts by sequestering drug, preventing it from reaching its intended target.;Furthermore, we investigated the utility of beta-1,3 glucan as a diagnostic marker for Candida biofilm infection. We found elevated serum glucan levels in animals with catheter biofilm infections compared to those with non-biofilm infections. These experiments identify a novel mechanism of resistance for Candida biofilms and a promising therapeutic and diagnostic target for these devastating infections.