Fungal infections represent an important health problem in terms of morbidity, mortality, and health care costs. Candida species are responsible for the largest number of fungal infections, with the majority attributed to Candida albicans and Candida glabrata. Both pathogens produce a similar array of superficial mucosal and life-threatening systemic infections;however, in contrast to C. albicans, C. glabrata is innately resistant to the most important triazole class of antifungals and lacks many of the virulence factors implicated in C. albicans invasion of host tissues. To compound this problem, several studies have documented a substantial increase in the incidence of C. glabrata infections. Despite this emergence, the biology of C. glabrata is largely unexplored and the basis for pathogenicity is unclear. Our long-term goal is to understand the molecular mechanisms required for C. glabrata colonization, persistence, and infection of mammalian tissues. In this R21 proposal, we will use emerging technologies to investigate the global transcript profile of C. glabrata during murine candidiasis and identify genes associated with the infectious process. To our knowledge, this will be the first study to identify the transcriptional signature of C. glabrata within an infected host. We hypothesize that C. glabrata possesses a repertoire of virulence-associated genes that are induced specifically in vivo during colonization and invasion of host tissues. We propose to: 1) identify C. glabrata genes expressed in vivo;2) determine the gene expression profile of C. glabrata colonizing and infecting murine tissue;3) identify a subset of genes induced specifically in a stage- and/or tissue-specific manner, and 4) establish a role for infection-associated genes in C. glabrata pathogenicity. Screening for host-induced genes represents a strategy to identify novel virulence factors and define global expression patterns relevant to pathogens. This study will provide insight into the diverse aspects of the fungal-host interaction and an improved understanding of the pathogenic processes contributing to disease.

Public Health Relevance

Our findings will impact current treatment strategies by identifying virulence factors that may be targeted for prophylactic and therapeutic intervention. Such knowledge will accelerate our ability to diagnose, treat, and control the number one fungal pathogen of humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI076721-01A2
Application #
7587764
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Duncan, Rory A
Project Start
2009-02-01
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2010-01-31
Support Year
1
Fiscal Year
2009
Total Cost
$219,000
Indirect Cost
Name
Medical University of South Carolina
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Westwater, Caroline; Schofield, David A (2012) Laser capture microdissection of Candida albicans from host tissue. Methods Mol Biol 845:397-409