Summary of Study ST002350

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001064. The data can be accessed directly via it's Project DOI: 10.21228/M85H6W This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study ID	ST002350
Study Title	Identify putative volatile biomarkers of Valley fever using a murine lung infection model
Study Type	Untargeted metabolomics
Study Summary	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 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 and C. posadasii Silveira via intranasal inoculation. We collected bronchoalveolar lavage fluid (BALF) for cytokine profiling and for untargeted volatile metabolomics via solid phase microextraction (SPME) and two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). We identified 36 volatile organic compounds (VOCs) that were significantly correlated to cytokine abundances and clustered mice by disease severity. These 36 VOCs were also able to separate mice with a moderate to high disease severity 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 disease severity.
Institute	Arizona State University
Department	School of Life Sciences
Laboratory	Bean Laboratory
Last Name	Bean
First Name	Heather
Address	PO Box 874501
Email	Heather.D.Bean@asu.edu
Phone	4807273395
Submit Date	2022-09-30
Raw Data Available	Yes
Raw Data File Type(s)	smp
Analysis Type Detail	GC-MS
Release Date	2023-01-02
Release Version	1

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Treatment:

Treatment ID:	TR002451
Treatment Summary:	Mice were anesthetized with ketamine/xylene (80/8 mg/kg) and intranasally inoculated with 100 arthroconidia of C. immitis strain RS (n=6) or C. posadasii strain Silveira (n=6) suspended in 30 μL phosphate-buffered saline (PBS), as described previously (22, 58). Control mice were inoculated with PBS alone (n=4). The mice were sacrificed at day 10 post-inoculation. The lungs were rinsed with 2 mL of PBS to collect bronchoalveolar lavage fluid (BALF), which were filtered with 0.22 μm Ultrafree® - MC centrifugal filter devices with Durapore® membrane (MilliporeSigma, Burlington, MA). One milliliter of each BALF sample was stored at –80°C for volatilomics analysis. Halt™ Protease Inhibitor Cocktail (10 μL/mL) was added to the remainder of each BALF sample for cytokine analysis. Spleen and brain were homogenized in 1 ml of sterile PBS followed by culture of 10-fold dilutions of each tissue on 2X GYE agar (2% glucose (VWR™, USA), 1% yeast extract (BD™, Franklin Lakes, New Jersey, USA, and 1.5% bacteriological agar (Difco, USA)) to assess fungal dissemination.

Treatment ID:

TR002451

Treatment Summary:

Mice were anesthetized with ketamine/xylene (80/8 mg/kg) and intranasally inoculated with 100 arthroconidia of C. immitis strain RS (n=6) or C. posadasii strain Silveira (n=6) suspended in 30 μL phosphate-buffered saline (PBS), as described previously (22, 58). Control mice were inoculated with PBS alone (n=4). The mice were sacrificed at day 10 post-inoculation. The lungs were rinsed with 2 mL of PBS to collect bronchoalveolar lavage fluid (BALF), which were filtered with 0.22 μm Ultrafree® - MC centrifugal filter devices with Durapore® membrane (MilliporeSigma, Burlington, MA). One milliliter of each BALF sample was stored at –80°C for volatilomics analysis. Halt™ Protease Inhibitor Cocktail (10 μL/mL) was added to the remainder of each BALF sample for cytokine analysis. Spleen and brain were homogenized in 1 ml of sterile PBS followed by culture of 10-fold dilutions of each tissue on 2X GYE agar (2% glucose (VWR™, USA), 1% yeast extract (BD™, Franklin Lakes, New Jersey, USA, and 1.5% bacteriological agar (Difco, USA)) to assess fungal dissemination.