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.
|Raman, Namrata; Marchillo, Karen; Lee, Myung-Ryul et al. (2016) Intraluminal Release of an Antifungal Î²-Peptide Enhances the Antifungal and Anti-Biofilm Activities of Multilayer-Coated Catheters in a Rat Model of Venous Catheter Infection. ACS Biomater Sci Eng 2:112-121|
|Nett, Jeniel E; Cabezas-Olcoz, Jonathan; Marchillo, Karen et al. (2016) Targeting Fibronectin To Disrupt In Vivo Candida albicans Biofilms. Antimicrob Agents Chemother 60:3152-5|
|Winter, Michael B; Salcedo, Eugenia C; Lohse, Matthew B et al. (2016) Global Identification of Biofilm-Specific Proteolysis in Candida albicans. MBio 7:|
|Dalal, Chiraj K; Zuleta, Ignacio A; Mitchell, Kaitlin F et al. (2016) Transcriptional rewiring over evolutionary timescales changes quantitative and qualitative properties of gene expression. Elife 5:|
|Nett, Jeniel E; Zarnowski, Robert; Cabezas-Olcoz, Jonathan et al. (2015) Host contributions to construction of three device-associated Candida albicans biofilms. Infect Immun 83:4630-8|
|Nett, Jeniel E; Andes, David R (2015) Fungal Biofilms: In Vivo Models for Discovery of Anti-Biofilm Drugs. Microbiol Spectr 3:|
|Fox, Emily P; Bui, Catherine K; Nett, Jeniel E et al. (2015) An expanded regulatory network temporally controls Candida albicans biofilm formation. Mol Microbiol 96:1226-39|
|Mitchell, Kaitlin F; Zarnowski, Robert; Sanchez, Hiram et al. (2015) Community participation in biofilm matrix assembly and function. Proc Natl Acad Sci U S A 112:4092-7|
|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|
|Desai, Jigar V; Mitchell, Aaron P; Andes, David R (2014) Fungal biofilms, drug resistance, and recurrent infection. Cold Spring Harb Perspect Med 4:|
Showing the most recent 10 out of 32 publications