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      Characterizing in vitro spherule morphogenesis of multiple strains of both species of Coccidioides

      1 , 2 , 1 , 2 , 3 , 1 , 2 , 3
      Medical Mycology
      Oxford University Press (OUP)

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          Abstract

          The disease San Joaquin Valley Fever (coccidioidomycosis) is caused by the inhalation of Coccidioides arthroconidia. In vivo , arthroconidia transform into pathogenic structures termed spherules. Exposure to the host milieu triggers spherule development; however, the molecular mechanisms responsible for the morphological shift are not well characterized. This study compared the morphogenesis of five strains of both species of Coccidioides in two media types to improve the in vitro model of dimorphism that can be easily reproduced, and is amenable to tissue culture. We also sought to establish a modern record of the morphological switch among commonly used lab strains through a detailed account of growth under various conditions. Spherules from five strains were grown in standard (Converse) and experimental media (RPMI-sph). Strain behavior was quantified by median spherule size and spherule concentration, beginning 3 days after inoculation and followed for 10 days of growth. There were significant differences observed among Coccidioides immitis and C. posadasii strains, as well as differences between the in vitro systems.

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          Most cited references20

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          Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

          The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism.
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            Enhanced Surveillance of Coccidioidomycosis, Arizona, USA, 2007–2008

            Additional public and provider education are needed to reduce delays in diagnosis.
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              A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB/c mice against coccidioidomycosis.

              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.
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                Author and article information

                Journal
                Medical Mycology
                Oxford University Press (OUP)
                1369-3786
                1460-2709
                June 2019
                June 01 2019
                July 20 2018
                June 2019
                June 01 2019
                July 20 2018
                : 57
                : 4
                : 478-488
                Affiliations
                [1 ]Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona
                [2 ]Pathogen Genomics Division, Translational Genomics Research Institute-North, Phoenix, Arizona
                [3 ]Valley Fever Center for Excellence, University of Arizona, Tucson, Arizona
                Article
                10.1093/mmy/myy049
                6506604
                30053114
                7adec859-db05-4a46-8c3a-b226e611feaf
                © 2018

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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