Coccidioides posadasii and Coccidioides immitis are both filamentous fungi and the causative agents of coccidioidomycosis, commonly known as Valley Fever. Over the past several decades, valley fever cases have increased dramatically, and the endemic range has expanded with recent verification of the organism in soil in Eastern Washington. These fungi are primary pathogens that can be responsible for morbidity and mortality in otherwise healthy patients, and disease can vary from asymptomatic to lethal. The underlying reasons for disease variation, and the role fungal genotype plays, represents a major gap in our knowledge. Our overall knowledge of the biology of Coccidioides is limited. The proposed project will define an entirely new life cycle stage, with high impact both for disease as well as understanding evolutionary potential. The existence of an ascospore that could be infectious, and have differential infection dynamics would explain at least in part, disease variation in human patients. Ascospores are also often resting structures in the environment that may provide environmental refugia for the fungus. Finally, recombined offspring may have novel phenoytpes that can adapt to new hosts and environments. The project will use standard mycological media and techniques to validate our preliminary results. Our approach will be focused on using genomic sequencing to define recombination patterns and frequency. Gaining an understanding of the mechanism of recombination, and potential new infectious spore type could greatly affect how disease prevalence and complications are viewed. This strategy will elucidate differences among recombinant Coccidioides strains for phenotypes such as stress tolerance, antifungal resistance, and pathogenicity, and determine if this is a mechanism of disease variation. The outcomes will fundamentally change our understanding of Coccidioides biology. The knowledge gained will allow for new genetic and mechanistic studies of Coccidioides.

Public Health Relevance

Coccidioides fungi cause coccidioidomycosis (valley fever) in otherwise healthy patients, and infections can vary from asymptomatic to lethal. Defining mechanisms of recombination could explain the lack of clonal population structure in this organism and help understand the role that fungal genotype plays in disease variation, which represents a major gap in our knowledge. Novel genotypes that arise from recombination events could also be a mechanism for expansion to new environments, as observed in the newly identified populations in Eastern Washington.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI128536-02
Application #
9613775
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Love, Dona
Project Start
2017-12-13
Project End
2019-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Northern Arizona University
Department
Miscellaneous
Type
Organized Research Units
DUNS #
806345542
City
Flagstaff
State
AZ
Country
United States
Zip Code
86011
Mead, Heather L; Teixeira, Marcus de Melo; Galgiani, John N et al. (2018) Characterizing in vitro spherule morphogenesis of multiple strains of both species of Coccidioides. Med Mycol :