abstract: Valley Fever (VF), is a potentially lethal fungal pneumonia caused by Coccidioides spp., which is estimated to cause ~15-30% of all community-acquired pneumonias in the highly endemic Greater Phoenix and Tucson areas of Arizona. However, an accurate antigen-based diagnostic is still lacking. In order to identify protein and glycan antigen biomarkers of infection, I used a combination of genomics, proteomics and glycomics analyses to provide evidence of genus-specific proteins and glycosylations. The next goal was to determine if Coccidioides-specific glycans were present in biological samples from VF patients. Urine collected from 77 humans and 63 dogs were enriched for glycans and evaluated by mass spectrometry for Coccidioides-specific glycans and evaluated against a panel of normal donor urines, urines from patients infected with other fungi, and fungal cultures from closely related pneumonia-causing fungi. A combination of 6 glycan biomarkers was 100% sensitive and 100% specific in the diagnosis of human VF subjects, while only 3 glycan biomarkers were needed for 100% sensitivity and 100 specificity in the diagnosis of dog VF subject. Additionally, a blinded trial of 23 human urine samples was correctly able to classify urine samples with 93.3% sensitivity and 100% specificity. The results of this research provides evidence that Coccidioides genus-specific glycosylations have potential as antigens in diagnostic assays. / Dissertation/Thesis / Doctoral Dissertation Microbiology 2019
| Identifer | oai:union.ndltd.org:asu.edu/item:53655 |
| Date | January 2019 |
| Contributors | Mitchell, Natalie Michelle (Author), Lake, Douglas F (Advisor), Bean, Heather D (Committee member), Grys, Thomas E (Committee member), Magee, Dewey M (Committee member), Arizona State University (Publisher) |
| Source Sets | Arizona State University |
| Language | English |
| Detected Language | English |
| Type | Doctoral Dissertation |
| Format | 201 pages |
| Rights | http://rightsstatements.org/vocab/InC/1.0/ |
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