The emerging fungal pathogen Candida auris has produced numerous outbreaks of invasive disease in hospitals worldwide. With mortality rates as high as 60%, the continued rise of this drug-resistant pathogen is alarming. Further understanding of the unexpected virulence of C. auris is desperately needed for the design of innovative therapeutic approaches. My laboratory?s long-term goal is to find new approaches to understand, detect, and treat invasive fungal infections. The objective of this application is to delineate how C. auris evades innate immunity and to develop a novel therapeutic strategy to circumvent this mechanism. We have found that neutrophils, leukocytes critical for control of many invasive fungal infections, fail to kill C. auris. We propose that uncovering the molecular mechanism of this immune evasion will identify new drug targets. Our preliminary data provide compelling evidence for the involvement of a C. auris cell wall component. Furthermore, we have identified a subset of neutrophils with enhanced antifungal activity. We plan to capitalize on this finding to delineate the molecular aspects of a successful neutrophil response against C. auris. This will not only shed light on the virulence of C. auris, but will also establish a platform for future neutrophil-based immunotherapies. We anticipate this approach will have broad implications for the treatment of a variety of drug-resistant or treatment-refractory invasive fungal infections.

Public Health Relevance

Candida auris has emerged as a global health threat, causing invasive disease with high mortality. Therapeutic options are limited for this multi-drug resistant pathogen. The proposed studies will uncover immune evasion mechanism(s) for C. auris and provide avenues for the development of therapeutics targeting the fungal and host components involved in this impairment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI145939-01A1
Application #
9969689
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Love, Dona
Project Start
2020-02-01
Project End
2025-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715