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Basic and Clinical Research on Coccidioides
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Basic and Clinical Research on Coccidioides

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 15642

Special Issue Editor

Dr. Bridget M. Barker

E-Mail Website
Guest Editor
Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011, USA
Interests: medical mycology

Special Issue Information

Dear Colleagues,

This Special Issue will compile topics from the annual Coccidioidomycosis Study Group meeting, held April 8–9, 2022, as well as other research on Coccidioides immitis, Coccidioides posadasii and coccidioidomycosis. Topics range from basic research on Coccidioides to clinical science and epidemiology. Primary research and reviews are welcome.

Dr. Bridget M. Barker
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fungal diseases
  • medical mycology
  • valley fever
  • coccidioidomycosis
  • Coccidioides immitis
  • Coccidioides posadasii

Published Papers (7 papers)

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10 pages, 2381 KiB  
Communication
Coccidioidal Pulmonary Cavitation: A New Age
by Lovedip Kooner, Augustine Munoz, Austin Garcia, Akriti Kaur, Rupam Sharma, Virginia Bustamante, Vishal Narang, George R. Thompson III, Rasha Kuran, Amir Berjis, Royce H. Johnson and Arash Heidari
J. Fungi 2023, 9(5), 561; https://doi.org/10.3390/jof9050561 - 12 May 2023
Cited by 1 | Viewed by 1550
Abstract
Coccidioides species are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with symptomatic pneumonic diseases as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either [...] Read more.
Coccidioides species are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with symptomatic pneumonic diseases as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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13 pages, 2594 KiB  
Article
Combating the Dust Devil: Utilizing Naturally Occurring Soil Microbes in Arizona to Inhibit the Growth of Coccidioides spp., the Causative Agent of Valley Fever
by Daniel R. Kollath, Matthew M. Morales, Ashley N. Itogawa, Dustin Mullaney, Naomi R. Lee and Bridget M. Barker
J. Fungi 2023, 9(3), 345; https://doi.org/10.3390/jof9030345 - 11 Mar 2023
Cited by 2 | Viewed by 2365
Abstract
The fungal disease Valley fever causes a significant medical and financial burden for affected people in the endemic region, and this burden is on the rise. Despite the medical importance of this disease, little is known about ecological factors that influence the geographic [...] Read more.
The fungal disease Valley fever causes a significant medical and financial burden for affected people in the endemic region, and this burden is on the rise. Despite the medical importance of this disease, little is known about ecological factors that influence the geographic point sources of high abundance of the pathogens Coccidioides posadasii and C. immitis, such as competition with co-occurring soil microbes. These “hot spots”, for instance, those in southern Arizona, are areas in which humans are at greater risk of being infected with the fungus due to consistent exposure. The aim of this study was to isolate native microbes from soils collected from Tucson, Arizona (endemic area for C. posadasii) and characterize their relationship (antagonistic, synergistic, or neutral) to the fungal pathogen with in vitro challenge assays. Secreted metabolites from the microbes were extracted and described using analytical techniques including high-performance liquid chromatography (HPLC) and mass spectrometry. Bacteria belonging to the genus Bacillus and fungi in the Fennellomyces and Ovatospora genera were shown to significantly decrease the growth of Coccidioides spp. In vitro. In contrast, other bacteria in the Brevibacillus genus, as well as one species of Bacillus bacteria, were shown to promote growth of Coccidioides when directly challenged. The metabolites secreted from the antagonistic bacteria were described using HPLC and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The microbes identified in this study as antagonists to Coccidioides and/or the metabolites they secrete have the potential to be used as natural biocontrol agents to limit the amount of fungal burden at geographic point sources, and therefore limit the potential for human infection. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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16 pages, 2315 KiB  
Article
Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model
by Emily A. Higgins Keppler, Marley C. Caballero Van Dyke, Heather L. Mead, Douglas F. Lake, D. Mitchell Magee, Bridget M. Barker and Heather D. Bean
J. Fungi 2023, 9(1), 115; https://doi.org/10.3390/jof9010115 - 14 Jan 2023
Cited by 3 | Viewed by 1784
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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16 pages, 4422 KiB  
Communication
Advocating for Coccidioidomycosis to Be a Reportable Disease Nationwide in the United States and Encouraging Disease Surveillance across North and South America
by Morgan E. Gorris, Karin Ardon-Dryer, Althea Campuzano, Laura R. Castañón-Olivares, Thomas E. Gill, Andrew Greene, Chiung-Yu Hung, Kimberly A. Kaufeld, Mark Lacy and Edith Sánchez-Paredes
J. Fungi 2023, 9(1), 83; https://doi.org/10.3390/jof9010083 - 5 Jan 2023
Cited by 3 | Viewed by 2667
Abstract
Coccidioidomycosis (Valley fever) has been a known health threat in the United States (US) since the 1930s, though not all states are currently required to report disease cases. Texas, one of the non-reporting states, is an example of where both historical and contemporary [...] Read more.
Coccidioidomycosis (Valley fever) has been a known health threat in the United States (US) since the 1930s, though not all states are currently required to report disease cases. Texas, one of the non-reporting states, is an example of where both historical and contemporary scientific evidence define the region as endemic, but we don’t know disease incidence in the state. Mandating coccidioidomycosis as a reportable disease across more US states would increase disease awareness, improve clinical outcomes, and help antifungal drug and vaccine development. It would also increase our understanding of where the disease is endemic and the relationships between environmental conditions and disease cases. This is true for other nations in North and South America that are also likely endemic for coccidioidomycosis, especially Mexico. This commentary advocates for US state and territory epidemiologists to define coccidioidomycosis as a reportable disease and encourages disease surveillance in other endemic regions across North and South America in order to protect human health and reduce disease burden. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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13 pages, 2706 KiB  
Article
Reactivation of Coccidioidomycosis in a Mouse Model of Asymptomatic Controlled Disease
by Lisa F. Shubitz, Daniel A. Powell, Sharon M. Dial, Christine D. Butkiewicz, Hien T. Trinh, Amy P. Hsu, Adam Buntzman, Jeffrey A. Frelinger and John N. Galgiani
J. Fungi 2022, 8(10), 991; https://doi.org/10.3390/jof8100991 - 21 Sep 2022
Cited by 2 | Viewed by 1619
Abstract
The majority of human coccidioidomycosis infections are asymptomatic or self-limited but may have sequestered spherules in highly structured granulomas. Under immunosuppression, reactivation of fungal growth can result in severe disease. B6D2F1 mice asymptomatically infected with C. posadasii strain 1038 were immunosuppressed with dexamethasone [...] Read more.
The majority of human coccidioidomycosis infections are asymptomatic or self-limited but may have sequestered spherules in highly structured granulomas. Under immunosuppression, reactivation of fungal growth can result in severe disease. B6D2F1 mice asymptomatically infected with C. posadasii strain 1038 were immunosuppressed with dexamethasone (DXM) in drinking water. Treated mice died 16–25 days later, while untreated mice survived (p < 0.001). Flow cytometry of lung granulomas on days 5, 10, 15, and 20 of DXM treatment showed immune cell populations decreased 0.5–1 log compared with untreated mice though neutrophils and CD19+IgD−IgM− cells rebounded by day 20. Histopathology demonstrated loss of granuloma structure by day 5 and increasing spherules through day 20. On day 20, T-cells were nearly absent and disorganized pyogranulomatous lesions included sheets of plasma cells and innumerable spherules. Mice given DXM for 14 days then stopped (DXM stop) survived 6 weeks (9/10). Lung fungal burdens were significantly lower (p = 0.0447) than mice that continued treatment (DXM cont) but higher than untreated mice. Histopathologically, DXM stop mice did not redevelop controlled granulomas by sacrifice, though T-cells were densely scattered throughout the lesions. This demonstrates a mouse model suitable for further study to understand the immunologic components responsible for maintenance control of coccidioidomycosis. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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14 pages, 7344 KiB  
Article
Characterization of the Growth and Morphology of a BSL-2 Coccidioides posadasii Strain That Persists in the Parasitic Life Cycle at Ambient CO2
by Javier A. Garcia, Kiem Vu, George R. Thompson III and Angie Gelli
J. Fungi 2022, 8(5), 455; https://doi.org/10.3390/jof8050455 - 28 Apr 2022
Cited by 1 | Viewed by 2375
Abstract
Coccidioides is a dimorphic fungus responsible for Valley Fever and is the cause of severe morbidity and mortality in the infected population. Although there is some insight into the genes, pathways, and growth media involved in the parasitic to saprophytic growth transition, the [...] Read more.
Coccidioides is a dimorphic fungus responsible for Valley Fever and is the cause of severe morbidity and mortality in the infected population. Although there is some insight into the genes, pathways, and growth media involved in the parasitic to saprophytic growth transition, the exact determinants that govern this switch are largely unknown. In this work, we examined the growth and morphology of a Coccidioides posadasii strain (C. posadasii S/E) that efficiently produces spherules and endospores and persists in the parasitic life cycle at ambient CO2. We demonstrated that C. posadasii S/E remains virulent in an insect infection model. Surprisingly, under spherule-inducing conditions, the C. posadasii S/E culture was found to be completely hyphal. Differential interference contrast (DIC) and transmission electron microscopy (TEM) revealed unexpected cellular changes in this strain including cell wall remodeling and formation of septal pores with Woronin bodies. Our study suggests that the C. posadasii S/E strain is a useful BSL-2 model for studying mechanisms underlying the parasitic to saprophytic growth transition—a morphological switch that can impact the pathogenicity of the organism in the host. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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8 pages, 216 KiB  
Brief Report
Fluconazole Failure in the Treatment of Coccidioidal Meningitis
by Simran Gupta, Neil M. Ampel, Molly Klanderman, Marie F. Grill and Janis E. Blair
J. Fungi 2022, 8(11), 1157; https://doi.org/10.3390/jof8111157 - 1 Nov 2022
Cited by 4 | Viewed by 2335
Abstract
Introduction: Coccidioidal meningitis (CM) is the most lethal form of disseminated coccidioidomycosis. Current guidelines recommend fluconazole as initial therapy but there has been a paucity of data regarding failure of fluconazole and optimal fluconazole dosage in the treatment of CM. We conducted this [...] Read more.
Introduction: Coccidioidal meningitis (CM) is the most lethal form of disseminated coccidioidomycosis. Current guidelines recommend fluconazole as initial therapy but there has been a paucity of data regarding failure of fluconazole and optimal fluconazole dosage in the treatment of CM. We conducted this study to understand risk factors for fluconazole failure. Methods: We conducted a single-center retrospective chart review of patients diagnosed with coccidioidal meningitis between 1 January 1988 and 15 May 2021. Relevant demographic and clinical variables were collected, along with outcomes including treatment failure and death at any point. Univariate tests were conducted using the chi-squared goodness of fit test and analysis of variance. Results: Among 71 patients who began treatment for CM with fluconazole, 22 (31%) developed worsening meningitis at a median time of 206 days. Longer time from symptom onset to diagnosis of CM was a risk factor for fluconazole failure. Although the absolute failure rate of fluconazole starting dose of 400 mg daily was higher than that of 800 mg daily, the differences did not achieve statistical significance (p = 0.39). Conclusion: Fluconazole failure is not uncommon in the treatment of CM. A dose of 800 mg daily was not superior to a dose of 400 mg daily. All patients on fluconazole for CM require close monitoring. Full article
(This article belongs to the Special Issue Basic and Clinical Research on Coccidioides)
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