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Garry T. Cole - One of the best experts on this subject based on the ideXlab platform.

  • preclinical identification of vaccine induced protective correlates in human leukocyte antigen expressing transgenic mice infected with Coccidioides posadasii
    Vaccine, 2016
    Co-Authors: Brady J Hurtgen, Garry T. Cole, Natalia Castrolopez, Maria Del Pilar Jimenezalzate, Chiung Yu Hung
    Abstract:

    There is an emerging interest to develop human vaccines against medically-important fungal pathogens and a need for a preclinical animal model to assess vaccine efficacies and protective correlates. HLA-DR4 (DRB1∗0401 allele) transgenic mice express a human major histocompatibility complex class II (MHC II) receptor in such a way that CD4+ T-cell response is solely restricted by this human molecule. In this study HLA-DR4 transgenic mice were immunized with a live-attenuated vaccine (ΔT) and challenged by the intranasal route with 50-70 Coccidioides posadasii spores, a potentially lethal dose. The same vaccination regimen offers 100% survival for C57BL/6 mice. Conversely, ΔT-vaccinated HLA-DR4 mice displayed 3 distinct manifestations of Coccidioides infection including 40% fatal acute (FAD), 30% disseminated (DD) and 30% pulmonary disease (PD). The latter 2 groups of mice had reduced loss of body weight and survived to at least 50days postchallenge (dpc). These results suggest that ΔT vaccinated HLA-DR4 mice activated heterogeneous immunity against pulmonary Coccidioides infection. Vaccinated HLA-DR4 mice displayed early expansion of Th1 and Th17 cells and recruitment of inflammatory innate cells into Coccidioides-infected lungs during the first 9dpc. While contraction rates of Th cells and the inflammatory response during 14-35dpc significantly differed among the 3 groups of vaccinated HLA-DR4 mice. The FAD group displayed a sharply reduced Th1 and Th17 response, while overwhelmingly recruiting neutrophils into lungs during 9-14days. The FAD group approached moribund by 14dpc. In contrast, vaccinated HLA-DR4 survivors gradually contracted Th cells and inflammatory response with the greatest rate in the PD group. While vaccinated HLA-DR4 mice are susceptible to Coccidioides infection, they are useful for evaluation of vaccine efficacy and identification of immunological correlates against this mycosis.

  • vaccinated c57bl 6 mice develop protective and memory t cell responses to Coccidioides posadasii infection in the absence of interleukin 10
    Infection and Immunity, 2014
    Co-Authors: Chiung Yu Hung, Natalia Castrolopez, Garry T. Cole
    Abstract:

    High concentrations of lung tissue-associated interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, correlate with susceptibility of mice to Coccidioides spp. infection. In this study, we found that macrophages, dendritic cells, neutrophils, and both CD8(+) and CD4(+) T cells recruited to Coccidioides posadasii-infected lungs of nonvaccinated and vaccinated mice contributed to the production of IL-10. The major IL-10-producing leukocytes were CD8(+) T cells, neutrophils, and macrophages in lungs of nonvaccinated mice, while both Foxp3(+) and Foxp3(-) subsets of IL-10(+) CD4(+) T cells were significantly elevated in vaccinated mice. Profiles of the recruited leukocytes in lungs revealed that only CD4(+) T cells were significantly increased in IL-10(-/-) knockout mice compared to their wild-type counterparts. Furthermore, ex vivo recall assays showed that CD4(+) T cells isolated from vaccinated IL-10(-/-) mice compared to vaccinated wild-type mice produced significantly higher amounts of IL-2, gamma interferon (IFN-γ), IL-4, IL-6, and IL-17A in the presence of a coccidioidal antigen, indicating that IL-10 suppresses Th1, Th2, and Th17 immunity to Coccidioides infection. Analysis of absolute numbers of CD44(+) CD62L(-) CD4(+) T effector memory T cells (TEM) and IFN-γ- and IL-17A-producing CD4(+) T cells in the lungs of Coccidioides-infected mice correlated with better fungal clearance in nonvaccinated IL-10(-/-) mice than in nonvaccinated wild-type mice. Our results suggest that IL-10 suppresses CD4(+) T-cell immunity in nonvaccinated mice during Coccidioides infection but does not impede the development of a memory response nor exacerbate immunopathology of vaccinated mice over at least a 4-month period after the last immunization.

  • extracellular ammonia at sites of pulmonary infection with Coccidioides posadasii contributes to severity of the respiratory disease
    Microbial Pathogenesis, 2013
    Co-Authors: Hua Zhang Wise, John W. Taylor, Chiung Yu Hung, Emily Whiston, Garry T. Cole
    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.

  • a genetically engineered live attenuated vaccine of Coccidioides posadasii protects balb c mice against coccidioidomycosis
    Infection and Immunity, 2009
    Co-Authors: Jianmin Xue, Chiung Yu Hung, Xia Chen, Dale M Selby, Garry T. Cole
    Abstract:

    Coccidioidomycosis (also known as San Joaquin Valley fever) is an occupational disease. Workers exposed to outdoor dust which contains spores of the soil-inhabiting fungus have a significantly increased risk of respiratory infection. In addition, people with compromised T-cell immunity, the elderly, and certain racial groups, particularly African-Americans and Filipinos, who live in regions of endemicity in the southwestern United States have an elevated incidence of symptomatic infection caused by inhalation of spores of Coccidioides posadasii or Coccidioides immitis. Recurring epidemics and escalation of medical costs have helped to motivate production of a vaccine against valley fever. The major focus has been the development of a defined, T-cell-reactive, recombinant protein vaccine. However, none of the products described to date have provided full protection to coccidioidal disease-susceptible BALB/c mice. Here we describe the first genetically engineered, live, attenuated vaccine that protects both BALB/c and C57BL/6 mice against coccidioidomycosis. Two chitinase genes (CTS2 and CTS3) were disrupted to yield the attenuated strain, which was unable to endosporulate and was no longer infectious. Vaccinated survivors mounted an immune response characterized by production of both T-helper-1- and T-helper-2-type cytokines. Histology revealed well-formed granulomas and markedly diminished inflammation. Significantly fewer organisms were observed in the lungs of survivors than in those of nonvaccinated mice. Additional investigations are required to further define the nature of the live, attenuated vaccine-induced immunity against Coccidioides infection.

  • evaluation of two homologous proline rich proteins of Coccidioides posadasii as candidate vaccines against coccidioidomycosis
    Infection and Immunity, 2007
    Co-Authors: Roger Alan Herr, Chiung Yu Hung, Garry T. Cole
    Abstract:

    Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential vaccines against this respiratory disease. A recombinant proline-rich antigen (rAg2/Pra) has been reported to be a leading vaccine candidate. However, contradictory results exist on the protection afforded by this antigen. Subcutaneous vaccination of either C57BL/6 or BALB/c mice with rAg2/Pra plus adjuvant followed by intraperitoneal challenge with C. posadasii resulted in a significant reduction of the fungal burden at 12 to 14 days postchallenge compared to that in nonvaccinated animals. Use of the same vaccination protocol followed by intranasal (i.n.) challenge of C57BL/6 mice with an equal number of organisms culminated in chronic pulmonary infection or death over a 90-day period. Early studies of Ag2/Pra suggested that it is a component of an immunogenic complex. We reveal in this study that C. posadasii produces a homolog of the reported proline-rich antigen, designated Prp2, which shows 69% protein sequence identity and 86% similarity to Ag2/Pra. Protection against i.n. challenge of C57BL/6 mice was evaluated by vaccination with the single bacterially expressed homolog, rAg2/Pra, or rPrp2 in combination with rAg2/Pra, each in the presence of the same adjuvant. The combined vaccine provided significantly better protection than either of the single recombinant protein vaccines. Results of enzyme-linked immunospot assays of the immunized mice revealed that the two proline-rich homologs contain unique T-cell epitopes. In combination, the recombinant proteins stimulate a more heterogeneous and protective T-cell repertoire than the monovalent vaccines.

John N Galgiani - One of the best experts on this subject based on the ideXlab platform.

  • a chronic murine disease model of coccidioidomycosis using Coccidioides posadasii strain 1038
    The Journal of Infectious Diseases, 2021
    Co-Authors: Lisa F. Shubitz, Marc J Orbach, Hien T. Trinh, Jeffrey A Frelinger, Daniel A Powell, Christine D Butkiewicz, Lourdes M Lewis, John N Galgiani
    Abstract:

    Murine infections with most Coccidioides spp. strains are lethal by 3 weeks, limiting the study of immune responses. Coccidioides posadasii, strain 1038 (Cp1038), while slowly lethal, resulted in protracted survival of C57BL/6 (B6) mice. In resistant (B6D2)F1/J mice, lung fungal burdens stabilized by week 4 without progression through week 16, better modeling human coccidioidal infections after their immunologic control. Immunodeficient tumor necrosis factor (Tnf) α knockout (KO) and interferon (Ifn) γ receptor 1 (Ifn-γr1) KO mice survived a median of 22.5 and 34 days, compared with 70 days in B6 mice (P = .001 and P < .01, respectively), though 14-day lung fungal burden studies showed little difference between Ifn-γr1 KO and B6 mice. B6 mice showed peak concentrations of key inflammatory lung cytokines, including interleukin 6, 23, and 17A, Tnf-α, and Ifn-γ, only after 4 weeks of infection. The slower progression in B6 and the acquired fungal burden stability in B6D2 mice after Cp1038 infection greatly increases the array of possible immunologic studies.

  • the rise of Coccidioides forces against the dust devil unleashed
    Frontiers in Immunology, 2019
    Co-Authors: Marley Caballero C Van Dyke, George Richard Thompson, John N Galgiani, Bridget M Barker
    Abstract:

    Coccidioidomycosis (Valley fever) is a fungal disease caused by the inhalation of Coccidioides posadasii or C. immitis. This neglected disease occurs in the desert areas of the western United States, most notably in California and Arizona, where infections continue to rise. Clinically, coccidioidomycosis ranges from asymptomatic to severe pulmonary disease and can disseminate to the brain, skin, bones, and elsewhere. New estimates suggest as many as 350,000 new cases of coccidioidomycosis occur in the United States each year. Thus, there is an urgent need for the development of a vaccine and new therapeutic drugs against Coccidioides infection. In this review, we discuss the battle against Coccidioides including the development of potential vaccines, the quest for new therapeutic drugs, and our current understanding of the protective host immune response to Coccidioides infection.

  • Strong population structure in Venezuelan populations of Coccidioides posadasii
    2019
    Co-Authors: Marcus De Melo Teixeira, John N Galgiani, George Richard Thompson, Primavera Alvarado, Chandler C. Roe, José Salvatori Patané, Jason W. Sahl, Paul Keim, Ana Litvintseva, Daniel R Matute
    Abstract:

    Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras, Guatemala and Venezuela. Comparative phylogenomic analyses of C. posadasii reveal that clinical strains from Venezuela are genetically distinct from the North American populations found in Arizona (AZ), Texas, Mexico, and the rest of South America (TX/MX/SA). We find evidence for admixture between the Venezuela and the North American populations of C. posadasii in Central America. As expected, the proportion of Venezuelan alleles in the admixed population decreases as latitude (and distance from Venezuela) increases. Our results indicate that the population in Venezuela may have been subjected to a recent bottleneck, and shows strong population structure. This analysis provides insight into potential for Coccidioides spp. to invade new regions.

  • viable spores of Coccidioides posadasii δcps1 are required for vaccination and provide long lasting immunity
    Vaccine, 2018
    Co-Authors: Lisa F. Shubitz, Marc J Orbach, Hien T. Trinh, Jeffrey A Frelinger, Daniel A Powell, Lourdes M Lewis, John N Galgiani
    Abstract:

    Coccidioidomycosis is a systemic fungal infection for which a vaccine has been sought for over fifty years. The avirulent Coccidioides posadasii strain, Δcps1, which is missing a 6 kb gene, showed significant protection in mice. These studies explore conditions of protection in mice and elucidate the immune response. Mice were vaccinated with different doses and viability states of Δcps1 spores, challenged with virulent C. posadasii, and sacrificed at various endpoints, dependent on experimental objectives. Tissues from vaccinated mice were harvested for in vitro elucidation of immune response. Vaccination with viable Δcps1 spores was required for protection from lethal challenge. Viable spore vaccination produced durable immunity, lasting at least 6 months, and prolonged survival (≥6 months). The C. posadasii vaccine strain also protected mice against C. immitis (survival ≥ 6 months). Cytokines from infected lungs of vaccinated mice in the first four days after Cp challenge showed significant increases of IFN-γ, as did stimulated CD4+ spleen cells from vaccinated mice. Transfer of CD4+ cells, but not CD8+ or B cells, reduced fungal burdens following challenge. IFN-γ from CD4+ cells in vaccinated mice indicates a Th1 response, which is critical for host control of coccidioidomycosis.

  • a Coccidioides posadasii cps1 deletion mutant is avirulent and protects mice from lethal infection
    Infection and Immunity, 2016
    Co-Authors: Hema Prasad Narra, John N Galgiani, Lisa F. Shubitz, Hien T. Trinh, Alejandra M Mandel, Kurt J Griffin, Adam Buntzman, Jeffrey A Frelinger, Marc J Orbach
    Abstract:

    ABSTRACT The CPS1 gene was identified as a virulence factor in the maize pathogen Cochliobolus heterostrophus. Hypothesizing that the homologous gene in Coccidioides posadasii could be important for virulence, we created a Δcps1 deletion mutant which was unable to cause disease in three strains of mice (C57BL/6, BALB/c, or the severely immunodeficient NOD-scid,γcnull [NSG]). Only a single colony was recovered from 1 of 60 C57BL/6 mice following intranasal infections of up to 4,400 spores. Following administration of very high doses (10,000 to 2.5 × 107 spores) to NSG and BALB/c mice, spherules were observed in lung sections at time points from day 3 to day 10 postinfection, but nearly all appeared degraded with infrequent endosporulation. Although the role of CPS1 in virulence is not understood, phenotypic alterations and transcription differences of at least 33 genes in the Δcps1 strain versus C. posadasii is consistent with both metabolic and regulatory functions for the gene. The in vitro phenotype of the Δcps1 strain showed slower growth of mycelia with delayed and lower spore production than C. posadasii, and in vitro spherules were smaller. Vaccination of C57BL/6 or BALB/c mice with live Δcps1 spores either intranasally, intraperitoneally, or subcutaneously resulted in over 95% survival with mean residual lung fungal burdens of

Marc J Orbach - One of the best experts on this subject based on the ideXlab platform.

  • a chronic murine disease model of coccidioidomycosis using Coccidioides posadasii strain 1038
    The Journal of Infectious Diseases, 2021
    Co-Authors: Lisa F. Shubitz, Marc J Orbach, Hien T. Trinh, Jeffrey A Frelinger, Daniel A Powell, Christine D Butkiewicz, Lourdes M Lewis, John N Galgiani
    Abstract:

    Murine infections with most Coccidioides spp. strains are lethal by 3 weeks, limiting the study of immune responses. Coccidioides posadasii, strain 1038 (Cp1038), while slowly lethal, resulted in protracted survival of C57BL/6 (B6) mice. In resistant (B6D2)F1/J mice, lung fungal burdens stabilized by week 4 without progression through week 16, better modeling human coccidioidal infections after their immunologic control. Immunodeficient tumor necrosis factor (Tnf) α knockout (KO) and interferon (Ifn) γ receptor 1 (Ifn-γr1) KO mice survived a median of 22.5 and 34 days, compared with 70 days in B6 mice (P = .001 and P < .01, respectively), though 14-day lung fungal burden studies showed little difference between Ifn-γr1 KO and B6 mice. B6 mice showed peak concentrations of key inflammatory lung cytokines, including interleukin 6, 23, and 17A, Tnf-α, and Ifn-γ, only after 4 weeks of infection. The slower progression in B6 and the acquired fungal burden stability in B6D2 mice after Cp1038 infection greatly increases the array of possible immunologic studies.

  • Coccidioides posadasii in a Dog With Cervical Dissemination Complicated by Esophageal Fistula.
    Frontiers in veterinary science, 2020
    Co-Authors: Adrien Izquierdo, Lisa F. Shubitz, Jared A. Jaffey, Stephanie D. Szabo, Jason Struthers, Ogi Okwumabua, Eric T. Hostnik, Mana Ohkura, Hien T. Trinh, Marc J Orbach
    Abstract:

    A 5-year-old male, neutered mixed breed dog with a history of a mass with an associated draining tract on the ventral cervical region was diagnosed with an esophageal fistula. The dog exhibited serosanguinous discharge from the draining tract, with enlarged left superficial cervical and mandibular lymph nodes, and was reported to have difficulty with deglutition of solid foods. Computed tomography revealed a communication of the draining tract with the esophagus along with enlargement of the left lateral retropharyngeal, left medial retropharyngeal, and mandibular lymph nodes. This prompted surgical exploration and debridement of the site, with closure of the esophageal fistula. Histopathology of thyroid gland, skeletal muscle, and adipose tissue obtained during surgical exploration showed spherules consistent with Coccidioides spp. infection. Antibody titers performed post-operatively were consistent with an active Coccidioides spp. Infection. By fungal culture and subsequent PCR and DNA sequencing, C. posadasii was identified as the species infecting the dog. Over the course of 85 days of antifungal therapy, discharge from the draining tract, lymphadenomegaly, and cutaneous and subcutaneous nodules resolved. In conclusion, this is the first reported case of disseminated coccidioidomycosis to the cervical region of a dog with involvement of the thyroid gland, skeletal muscle, adipose tissue, connective tissue, and secondary esophageal fistula. Coccidioides spp. infections should be considered a differential diagnosis in unusual cases for dogs that live in or have traveled to endemic areas.

  • viable spores of Coccidioides posadasii δcps1 are required for vaccination and provide long lasting immunity
    Vaccine, 2018
    Co-Authors: Lisa F. Shubitz, Marc J Orbach, Hien T. Trinh, Jeffrey A Frelinger, Daniel A Powell, Lourdes M Lewis, John N Galgiani
    Abstract:

    Coccidioidomycosis is a systemic fungal infection for which a vaccine has been sought for over fifty years. The avirulent Coccidioides posadasii strain, Δcps1, which is missing a 6 kb gene, showed significant protection in mice. These studies explore conditions of protection in mice and elucidate the immune response. Mice were vaccinated with different doses and viability states of Δcps1 spores, challenged with virulent C. posadasii, and sacrificed at various endpoints, dependent on experimental objectives. Tissues from vaccinated mice were harvested for in vitro elucidation of immune response. Vaccination with viable Δcps1 spores was required for protection from lethal challenge. Viable spore vaccination produced durable immunity, lasting at least 6 months, and prolonged survival (≥6 months). The C. posadasii vaccine strain also protected mice against C. immitis (survival ≥ 6 months). Cytokines from infected lungs of vaccinated mice in the first four days after Cp challenge showed significant increases of IFN-γ, as did stimulated CD4+ spleen cells from vaccinated mice. Transfer of CD4+ cells, but not CD8+ or B cells, reduced fungal burdens following challenge. IFN-γ from CD4+ cells in vaccinated mice indicates a Th1 response, which is critical for host control of coccidioidomycosis.

  • a Coccidioides posadasii cps1 deletion mutant is avirulent and protects mice from lethal infection
    Infection and Immunity, 2016
    Co-Authors: Hema Prasad Narra, John N Galgiani, Lisa F. Shubitz, Hien T. Trinh, Alejandra M Mandel, Kurt J Griffin, Adam Buntzman, Jeffrey A Frelinger, Marc J Orbach
    Abstract:

    ABSTRACT The CPS1 gene was identified as a virulence factor in the maize pathogen Cochliobolus heterostrophus. Hypothesizing that the homologous gene in Coccidioides posadasii could be important for virulence, we created a Δcps1 deletion mutant which was unable to cause disease in three strains of mice (C57BL/6, BALB/c, or the severely immunodeficient NOD-scid,γcnull [NSG]). Only a single colony was recovered from 1 of 60 C57BL/6 mice following intranasal infections of up to 4,400 spores. Following administration of very high doses (10,000 to 2.5 × 107 spores) to NSG and BALB/c mice, spherules were observed in lung sections at time points from day 3 to day 10 postinfection, but nearly all appeared degraded with infrequent endosporulation. Although the role of CPS1 in virulence is not understood, phenotypic alterations and transcription differences of at least 33 genes in the Δcps1 strain versus C. posadasii is consistent with both metabolic and regulatory functions for the gene. The in vitro phenotype of the Δcps1 strain showed slower growth of mycelia with delayed and lower spore production than C. posadasii, and in vitro spherules were smaller. Vaccination of C57BL/6 or BALB/c mice with live Δcps1 spores either intranasally, intraperitoneally, or subcutaneously resulted in over 95% survival with mean residual lung fungal burdens of

  • Detection and phylogenetic analysis of Coccidioides posadasii in Arizona soil samples
    Fungal Ecology, 2012
    Co-Authors: Bridget M Barker, Joseph A. Tabor, Lisa F. Shubitz, Robert Perrill, Marc J Orbach
    Abstract:

    Reports of coccidioidomycosis are on the rise in the southwestern US. However, the ecology of the pathogen, Coccidioides, remains obscure and there is limited knowledge of the environmental antecedents of disease outbreaks. Detection of the fungus in the environment remains a critical challenge to modeling the source of disease. Using BALB/c mice as a biosensor, 8.9 % of soils analyzed from the Tucson area (Pima County, Arizona) were found to contain the pathogen. The genotypes of 66 Coccidioides strains, recovered from 11 soils, were determined with diagnostic microsatellite loci. Comparison of these genotypes to clinical isolates revealed all were Coccidioides posadasii and they grouped with Arizona isolates. Among sites where multiple strains were recovered, two indicated a clonal population, while others yielded a diversity of genotypes. A secondary goal of this research was to assess applicability of PCR, with its potential for high-throughput screening, as a method for identifying Coccidioides-containing soils.

Bridget M Barker - One of the best experts on this subject based on the ideXlab platform.

  • Structural characterization and evolutionary analyses of the Coccidioides immitis and Coccidioides posadasii mitochondrial genomes
    2020
    Co-Authors: Marcus De Melo Teixeira, Jason E Stajich, B Franz Lang, Daniel R Matute, Bridget M Barker
    Abstract:

    Fungal mitochondrial genomes encode for genes involved in crucial cellular processes, such as oxidative phosphorylation and mitochondrial translation, and these genes have been used as molecular markers for population genetics studies. Coccidioides immitis and C. posadasii are endemic fungal pathogens that cause coccidioidomycosis in arid regions across both American continents. To date, almost one hundred Coccidioides strains have been sequenced. The focus of these studies has been exclusively to infer patterns of variation of nuclear genomes (nucDNA). However, their mitochondrial genomes (mtDNA) have not been studied. In this report, we describe the assembly and annotation of mitochondrial reference genomes for two representative strains of C. posadasii and C. immitis, as well as assess population variation among 77 published genomes. The circular-mapping mtDNA molecules are 68.2 Kb in C. immitis and 75.1 Kb in C. posadasii. We identified the fourteen mitochondrial protein-coding genes common to most fungal mitochondria, including genes encoding the small and large ribosomal RNAs (rns and rnl), the RNA subunit of RNAse P (rnpB), and 26 tRNAs organized in polycistronic transcription units, which are mostly syntenic across different populations and species of Coccidioides. Both Coccidioides species are characterized by a large number of group I and II introns, harboring twice the number of elements as compared to closely related Onygenales. The introns contain complete or truncated ORFs with high similarity to homing endonucleases of the LAGLIDADG and GIY-YIG families. Phylogenetic comparison of the mtDNA and nucDNA genomes shows discordance, possibly due to differences in patterns of inheritance. In summary, this work represents the first complete assessment of mitochondrial genomes among several isolates of both species of Coccidioides, and provides a foundation for future functional work.

  • the rise of Coccidioides forces against the dust devil unleashed
    Frontiers in Immunology, 2019
    Co-Authors: Marley Caballero C Van Dyke, George Richard Thompson, John N Galgiani, Bridget M Barker
    Abstract:

    Coccidioidomycosis (Valley fever) is a fungal disease caused by the inhalation of Coccidioides posadasii or C. immitis. This neglected disease occurs in the desert areas of the western United States, most notably in California and Arizona, where infections continue to rise. Clinically, coccidioidomycosis ranges from asymptomatic to severe pulmonary disease and can disseminate to the brain, skin, bones, and elsewhere. New estimates suggest as many as 350,000 new cases of coccidioidomycosis occur in the United States each year. Thus, there is an urgent need for the development of a vaccine and new therapeutic drugs against Coccidioides infection. In this review, we discuss the battle against Coccidioides including the development of potential vaccines, the quest for new therapeutic drugs, and our current understanding of the protective host immune response to Coccidioides infection.

  • Heat Inactivation of Coccidioides posadasii and Coccidioides immitis for Use in Lower Biosafety Containment
    Applied biosafety : journal of the American Biological Safety Association, 2019
    Co-Authors: Heather L. Mead, Austin V. Blackmon, Amy J. Vogler, Bridget M Barker
    Abstract:

    Introduction:The difficulty involved in obtaining sufficient intact genomic deoxyribonucleic acid (DNA) from Coccidioides spp for downstream applications using published protocols prompted the expl...

  • the mysterious desert dwellers Coccidioides immitis and Coccidioides posadasii causative fungal agents of coccidioidomycosis
    Virulence, 2019
    Co-Authors: Daniel R Kollath, Karis J Miller, Bridget M Barker
    Abstract:

    The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to semia...

  • the mysterious desert dwellers Coccidioides immitis and Coccidioides posadasii causative fungal agents of coccidioidomycosis
    Virulence, 2019
    Co-Authors: Daniel R Kollath, Karis J Miller, Bridget M Barker
    Abstract:

    The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to semiarid alkaline soils throughout western North America and into Central and South America. Regions in the United States, with highest prevalence of disease, include California, Arizona, and Texas. The Mexican states of Baja California, Coahuila, Sonora, and Neuvo Leon currently have the highest skin test positive results. Central America contains isolated endemic areas in Guatemala and Honduras. South America has isolated regions of high endemicity including areas of Colombia, Venezuela, Argentina, Paraguay, and Brazil. Although approximately 15,000 cases per year are reported in the United States, actual disease burden is estimated to be in the hundreds of thousands, as only California and Arizona have dedicated public health outreach, and report and track disease reliably. In this review, we survey genomics, epidemiology, ecology, and summarize aspects of disease, diagnosis, prevention, and treatment.

Christine C Ginocchio - One of the best experts on this subject based on the ideXlab platform.