. are an increasingly common cause of bloodstream infections in hospitalized patients 
. This rise in incidence is at least in part related to the organism's ability to produce biofilm infections on medical devices 
. A biofilm is a community of microbes attached to a surface and encased in an extracellular matrix 
. The biofilm lifestyle is a common form of growth in nature and the most common cause of infection in humans. The most troublesome characteristic of biofilms is that they are up to 1,000-fold more resistant to common antifungals than their planktonic counterparts, even without accumulation of specific drug-resistance genes 
. This lack of effective therapy contributes to dismal outcomes for patients with invasive candidiasis, including death in up to 40% of patients. Delineating the mechanisms of biofilm formation and associated treatment resistance is one method of identifying optimal management strategies and therapeutics of this devastating infectious disease.
The focus of our investigations is the construction and configuration of the extracellular biofilm matrix, one of the properties that distinguishes biofilm from planktonic growth 
. The function of matrix remains incompletely understood, but previous investigations have identified roles such as providing infrastructure for biofilm accumulation, controlling disaggregation, and granting protection from antimicrobial drugs and the host immune system 
. Although the complete composition of the C. albicans
biofilm matrix has yet to be fully elucidated, studies have identified the inclusion of carbohydrates, proteins, and nucleic acids components 
. The goal of the present studies was to identify genes that control matrix delivery. We hypothesized that this process involves a biofilm-specific pathway composed of enzymes capable of modifying matrix carbohydrates. This hypothesis is based on two findings. First, one of the carbohydrates, β-1,3 glucan, has been linked to overall matrix production and drug resistance through glucan synthase gene FKS1
(common nomenclature for the gene GSC1
. Second, microarray analysis of in vivo rat catheter biofilms demonstrated transcript abundance of multiple glucan modification genes 
Here we use a candidate gene set to investigate the role of glucan matrix delivery. The gene set was selected to include glucan modification genes which demonstrated transcriptional upregulation in a rat venous catheter biofilm model. In addition, we included gene products which are known or hypothesized to utilize β-1,3 glucan as a substrate 
. Many of the selected genes had been shown previously to function in planktonic cell wall synthesis and remodeling 
. We constructed gene mutants and screened for biofilm formation, matrix delivery and antifungal drug susceptibility.
In the current studies we describe the role of three glucan modifying genes for glucan delivery and matrix incorporation. These gene products encode two glucanosyltranferases (BGL2
) and a glucanase (XOG1
), respectively 
. Each appears necessary for modification and delivery of carbohydrate to the mature biofilm matrix. Without delivery and accumulation of matrix glucan, the biofilms exhibit enhanced susceptibility to antifungal drugs. As the biofilm matrix is integral for biofilm maintenance and drug resistance, these delivery enzymes provide promising targets for anti-biofilm drug development.