Cargando…

Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model

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 sever...

Descripción completa

Detalles Bibliográficos
Autores principales: Higgins Keppler, Emily A., Van Dyke, Marley C. Caballero, Mead, Heather L., Lake, Douglas F., Magee, D. Mitchell, Barker, Bridget M., Bean, Heather D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864585/
https://www.ncbi.nlm.nih.gov/pubmed/36675936
http://dx.doi.org/10.3390/jof9010115
_version_ 1784875619501211648
author Higgins Keppler, Emily A.
Van Dyke, Marley C. Caballero
Mead, Heather L.
Lake, Douglas F.
Magee, D. Mitchell
Barker, Bridget M.
Bean, Heather D.
author_facet Higgins Keppler, Emily A.
Van Dyke, Marley C. Caballero
Mead, Heather L.
Lake, Douglas F.
Magee, D. Mitchell
Barker, Bridget M.
Bean, Heather D.
author_sort Higgins Keppler, Emily A.
collection PubMed
description 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 (GC×GC-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.
format Online
Article
Text
id pubmed-9864585
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98645852023-01-22 Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model Higgins Keppler, Emily A. Van Dyke, Marley C. Caballero Mead, Heather L. Lake, Douglas F. Magee, D. Mitchell Barker, Bridget M. Bean, Heather D. J Fungi (Basel) Article 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 (GC×GC-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. MDPI 2023-01-14 /pmc/articles/PMC9864585/ /pubmed/36675936 http://dx.doi.org/10.3390/jof9010115 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Higgins Keppler, Emily A.
Van Dyke, Marley C. Caballero
Mead, Heather L.
Lake, Douglas F.
Magee, D. Mitchell
Barker, Bridget M.
Bean, Heather D.
Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
title Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
title_full Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
title_fullStr Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
title_full_unstemmed Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
title_short Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
title_sort volatile metabolites in lavage fluid are correlated with cytokine production in a valley fever murine model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864585/
https://www.ncbi.nlm.nih.gov/pubmed/36675936
http://dx.doi.org/10.3390/jof9010115
work_keys_str_mv AT higginskeppleremilya volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel
AT vandykemarleyccaballero volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel
AT meadheatherl volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel
AT lakedouglasf volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel
AT mageedmitchell volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel
AT barkerbridgetm volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel
AT beanheatherd volatilemetabolitesinlavagefluidarecorrelatedwithcytokineproductioninavalleyfevermurinemodel