One of Candida albicans most impressive virulence attributes is the ability to propagate as a biofilm when attached to a medical device, such as a venous catheter. This critical factor alone is responsible for the majority of invasive and persistent disease. As conventional antimicrobials are ineffective for treatment of these life-threatening infections, further understanding of the biofilm lifestyle and how the cells survive drug therapy is desperately needed. The microbe-derived extracellular matrix, a distinguishing feature of biofilms, has been linked to several roles in biofilm pathogenesis. The proposed investigation capitalizes on our progress during the last funding period that identified the role o one matrix component, ?-1,3 glucan, for biofilm resistance and dispersion. Our excitement for future investigation is based upon two unexpected observations. First, we were surprised to find an abundance of two additional matrix polysaccharides, ?-1,6 glucan and ?-mannan. Second, we demonstrated an interaction among these matrix components. Our major objectives now are 1] to define the genetic pathways governing production, delivery, and maturation of the entire complement of polysaccharide matrix and 2] to discern how these matrix components function both individually and in a coordinated fashion during biofilm pathogenesis.
Candida frequently forms biofilms on the surface of medical devices. There are no effective drug therapies for these commonly lethal fungal infections. The proposed studies will uncover mechanisms that permit Candida to proliferate on implanted devices despite extraordinarily high drug concentrations. Our goal is to discover targets for development of innovative therapeutic agents.
|Nobile, Clarissa J; Fox, Emily P; Hartooni, Nairi et al. (2014) A histone deacetylase complex mediates biofilm dispersal and drug resistance in Candida albicans. MBio 5:e01201-14|
|Nett, Jeniel E; Brooks, Erin G; Cabezas-Olcoz, Jonathan et al. (2014) Rat indwelling urinary catheter model of Candida albicans biofilm infection. Infect Immun 82:4931-40|
|Holland, Linda M; Schröder, Markus S; Turner, Siobhán A et al. (2014) Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans. PLoS Pathog 10:e1004365|
|Zarnowski, Robert; Westler, William M; Lacmbouh, Ghislain Ade et al. (2014) Novel entries in a fungal biofilm matrix encyclopedia. MBio 5:e01333-14|
|Desai, Jigar V; Mitchell, Aaron P; Andes, David R (2014) Fungal biofilms, drug resistance, and recurrent infection. Cold Spring Harb Perspect Med 4:|
|Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A et al. (2013) Mechanisms of Candida biofilm drug resistance. Future Microbiol 8:1325-37|
|Mitchell, K F; Taff, H T; Cuevas, M A et al. (2013) Role of matrix ?-1,3 glucan in antifungal resistance of non-albicans Candida biofilms. Antimicrob Agents Chemother 57:1918-20|
|Nobile, Clarissa J; Fox, Emily P; Nett, Jeniel E et al. (2012) A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148:126-38|
|Nett, Jeniel E; Marchillo, Karen; Andes, David R (2012) Modeling of fungal biofilms using a rat central vein catheter. Methods Mol Biol 845:547-56|
|Taff, Heather T; Nett, Jeniel E; Andes, David R (2012) Comparative analysis of Candida biofilm quantitation assays. Med Mycol 50:214-8|
Showing the most recent 10 out of 16 publications