They belong to the order Onygenales and are members of the phylum Ascomycota. Both Coccidioides species are indigenous to the New World where they grow as molds in the alkaline desert soils, primarily in North America, but also in scattered desert

areas in South America [2]. These organisms are pathogenic for mammals (including humans), and it is estimated that there are ~150,000 infections annually in the US, primarily in the southwestern region [3]. The soil form of these fungi is a mold that produces infectious spores (arthroconidia) that can become airborne if the soil is disturbed. Arthroconidia are ~ 4 micron in diameter and when inhaled into buy MK0683 the lung they can cause pneumonia. Inside the host, under the influence of temperature and partial pressure of CO2, the organism undergoes a remarkable transformation into spherules, the pathognomonic tissue form of Coccidioides. Arthroconidia first round up and then they start to enlarge and transform. As they grow their cytoplasm undergoes internal segmentation to produce hundreds of endospores that are released when a spherule ruptures [4, 5]. These endospores in turn enlarge into spherules and replication continues until the host immune response controls the process or the host dies. The two species of Coccidioides have the same life cycle and there is no known difference in the clinical

disease caused by infection with the two

GSI-IX species. The natural history of coccidioidomycosis PAK5 is very variable. About 60% of infections are mild and go undiagnosed, but in Arizona (a hyper-endemic region) coccidioidomycosis is a leading cause of symptomatic pneumonia [6]. Most of those infections resolve spontaneously but they can leave residual solitary granulomas or occasionally thin-walled cavities. In about 5% of cases infection does not remain confined to the lung and spreads to extra-pulmonary sites. This spread can be an overwhelming, life threatening process, or it can manifest as isolated skin, bone, joint, or meningeal infections. The last is uniformly fatal without treatment. Most people with Selleckchem eFT-508 dissemination suffer from prolonged and debilitating infections that are difficult to treat [7]. People who are immunosuppressed, either by disease or iatrogenically, are at high risk for dissemination but the majority of disseminated cases occur in previously healthy individuals with no known immunological defects [8]. As with all the dimorphic pathogenic fungi (Blastomyces dermatitidis, Histoplasma capsulatum, Paracoccidioides brasiliensis and Sporothrix schenckii) the pathogenic form in tissue looks completely different form the saprobic mycelial form found in the environment. In coccidioidomycosis spherule formation is required for pathogenicity [9], as exemplified by two mutant strains [10, 11].