ArticleMicrobial pathogenesis
Extracellular ammonia at sites of pulmonary infection with Coccidioides posadasii contributes to severity of the respiratory disease.
Article in Microbial pathogenesis. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- "Select and Resequence" Methods Enable a Genome-Wide Association Study of the Dimorphic Human Fungal Pathogen Coccidioides posadasii.Genome biology and evolution · 2025Article
- Inferring the composition of a mixed culture of natural microbial isolates by deep sequencing.bioRxiv : the preprint server for biology · 2024Article
- Coccidioides Species: A Review of Basic Research: 2022.Journal of fungi (Basel, Switzerland) · 2022Review
- Toxic Metabolites and Inborn Errors of Amino Acid Metabolism: What One Informs about the Other.Metabolites · 2022Review
- Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus onFrontiers in medicine · 2022Review
- The Known Unknowns of the Immune Response toJournal of fungi (Basel, Switzerland) · 2021Review
- Transcriptional Analysis ofJournal of fungi (Basel, Switzerland) · 2021Article
- A Review ofCurrent clinical microbiology reports · 2021Review
- Proper Care and Feeding of Coccidioides: A Laboratorian's Guide to Cultivating the Dimorphic Stages of C. immitis and C. posadasii.Current protocols in microbiology · 2020Article
- Defining Critical Genes During Spherule Remodeling and Endospore Development in the Fungal Pathogen,Frontiers in genetics · 2020Article
- Early Events in Coccidioidomycosis.Clinical microbiology reviews · 2019Review
- Invasive endemic fungi of the Western Hemisphere.Virulence · 2019Article
- Coccidioidomycosis: Epidemiology, Fungal Pathogenesis, and Therapeutic Development.Current tropical medicine reports · 2019Article
- Differentiating lung cancer and infection based on measurements of extracellular pH with acidoCEST MRI.Scientific reports · 2019Article
- How Environmental Fungi Cause a Range of Clinical Outcomes in Susceptible Hosts.Journal of molecular biology · 2019Review
- A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo pH.Magnetic resonance in medicine · 2018Article
- Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity.Virulence · 2018Review
- Ammonia toxicity: from head to toe?Metabolic brain disease · 2017Review
- Environmental pH modulation by pathogenic fungi as a strategy to conquer the host.PLoS pathogens · 2017Review
- Fungal Dimorphism and Virulence: Molecular Mechanisms for Temperature Adaptation, Immune Evasion, and In Vivo Survival.Mediators of inflammation · 2017Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Coccidioides is the causative agent of a potentially life-threatening respiratory disease of humans. A feature of this mycosis is that pH measurements of the microenvironment of pulmonary abscesses are consistently alkaline due to ammonia production during the parasitic cycle. We previously showed that enzymatically active urease is partly responsible for elevated concentrations of extracellular ammonia at sites of lung infection and contributes to both localized host tissue damage and exacerbation of the respiratory disease in BALB/c mice. Disruption of the urease gene (URE) of Coccidioides posadasii only partially reduced the amount of ammonia detected during in vitro growth of the parasitic phase, suggesting that other ammonia-producing pathways exist that may also contribute to the virulence of this pathogen. Ureidoglycolate hydrolase (Ugh) expressed by bacteria, fungi and higher plants catalyzes the hydrolysis of ureidoglycolate to yield glyoxylate and the release CO2 and ammonia. This enzymatic pathway is absent in mice and humans. Ureidoglycolate hydrolase gene deletions were conducted in a wild type (WT) isolate of C. posadasii as well as the previously generated Δure knock-out strain. Restorations of UGH in the mutant stains were performed to generate and evaluate the respective revertants. The double mutant revealed a marked decrease in the amount of extracellular ammonia without loss of reproductive competence in vitro compared to both the WT and Δure parental strains. BALB/c mice challenged intranasally with the Δugh/Δure mutant showed 90% survival after 30 days, decreased fungal burden, and well-organized pulmonary granulomas. We conclude that loss of both Ugh and Ure activity significantly reduced the virulence of this fungal pathogen.
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