| Title: | Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model |
| Author(s): | Higgins Keppler EA; Van Dyke MCC; Mead HL; Lake DF; Magee DM; Barker BM; Bean HD; |
| Address: | "School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA. Center for Fundamental and Applied Microbiomics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011, USA. Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA" |
| ISSN/ISBN: | 2309-608X (Electronic) 2309-608X (Linking) |
| Abstract: | "Coccidioides immitis and Coccidioides posadasii are soil-dwelling fungi of arid regions in North and South America that are responsible for Valley fever (coccidioidomycosis). Forty percent of patients with Valley fever exhibit symptoms ranging from mild, self-limiting respiratory infections to severe, life-threatening pneumonia that requires treatment. Misdiagnosis as bacterial pneumonia commonly occurs in symptomatic Valley fever cases, resulting in inappropriate treatment with antibiotics, increased medical costs, and delay in diagnosis. In this proof-of-concept study, we explored the feasibility of developing breath-based diagnostics for Valley fever using a murine lung infection model. To investigate potential volatile biomarkers of Valley fever that arise from host-pathogen interactions, we infected C57BL/6J mice with C. immitis RS (n = 6), C. posadasii Silveira (n = 6), or phosphate-buffered saline (n = 4) via intranasal inoculation. We measured fungal dissemination and collected bronchoalveolar lavage fluid (BALF) for cytokine profiling and for untargeted volatile metabolomics via solid-phase microextraction (SPME) and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS). We identified 36 volatile organic compounds (VOCs) that were significantly correlated (p < 0.05) with cytokine abundance. These 36 VOCs clustered mice by their cytokine production and were also able to separate mice with moderate-to-high cytokine production by infection strain. The data presented here show that Coccidioides and/or the host produce volatile metabolites that may yield biomarkers for a Valley fever breath test that can detect coccidioidal infection and provide clinically relevant information on primary pulmonary disease severity" |
| Keywords: | GCxGC Valley fever biomarkers coccidioidomycosis comprehensive two-dimensional gas chromatography fungal pneumonia mouse model untargeted metabolomics; |
| Notes: | "PubMed-not-MEDLINEHiggins Keppler, Emily A Van Dyke, Marley C Caballero Mead, Heather L Lake, Douglas F Magee, D Mitchell Barker, Bridget M Bean, Heather D eng ADHS18-198861/Arizona Biomedical Research Centre/ Switzerland 2023/01/22 J Fungi (Basel). 2023 Jan 14; 9(1):115. doi: 10.3390/jof9010115" |
