Gene expression in human fungal pathogen Coccidioides immitis changes as mycelia differentiate into spherules and mature

BACKGROUND:Coccidioides immitis is a dimorphic fungus that causes disease in mammals, including human beings. It grows as a mycelium containing arthroconidia in the soil and in the host arthroconidia differentiates into a unique structure called a spherule. We used a custom open reading frame oligonucleotide microarray to compare the transcriptome of C. immitis mycelia with early (day 2) and late stage (day 8) spherules grown in vitro. All hybridizations were done in quadruplicate and stringent criteria were used to identify significantly differentially expressed genes.RESULTS:22% of C. immitis genes were differentially expressed in either day 2 or day 8 spherules compared to mycelia, and about 12% of genes were differentially expressed comparing the two spherule time points. Oxireductases, including an extracellular superoxide dismutase, were upregulated in spherules and they may be important for defense against oxidative stress. Many signal transduction molecules, including pleckstrin domain proteins, protein kinases and transcription factors were downregulated in day 2 spherules. Several genes involved in sulfur metabolism were downregulated in day 8 spherules compared to day 2 spherules. Transcription of amylase and ? (1,3) glucan synthase was upregulated in spherules; these genes have been found to be important for differentiation to yeast in Histoplasma. There were two homologs of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD); transcription of one was up- and the other downregulated. We tested the effect of a 4-HPPD inhibitor, nitisinone, on mycelial and spherule growth and found that it inhibited mycelial but not spherule growth.CONCLUSIONS:Transcription of many genes was differentially expressed in the process of arthroconidia to spherule conversion and spherule maturation, as would be expected given the magnitude of the morphologic change. The transcription profile of early stage (day 2) spherules was different than late stage (day 8) endosporulating spherules. In addition, very few genes that are important for spore to yeast conversion in other dimorphic fungi are differentially expressed in C. immitis mycelia and spherules suggesting that dimorphic fungi may have evolved different mechanisms to differentiate from mycelia to tissue invasive forms

Fluctuations in Climate and Incidence of Coccidioidomycosis in Kern County, California: A Review

Coccidioidomycosis (Valley Fever) is a fungal infection found in the southwestern United States, northern Mexico, and some places in Central and South America. The fungi that cause it (Coccidioides immitis and Coccidioides posadasii) are normally soil dwelling, but, if disturbed, become airborne and infect the host when their spores are inhaled. It is thus natural to surmise that weather conditions, which foster the growth and dispersal of Coccidioides, must have an effect on the number of cases in the endemic areas. This article reviews our attempts to date at quantifying this relationship in Kern County, California (where C. immitisis endemic). We have examined the effect on incidence resulting from precipitation, surface temperature, and wind speed. We have performed our studies by means of a simple linear correlation analysis, and by a generalized autoregressive moving average model. Our first analysis suggests that linear correlations between climatic parameters and incidence are weak; our second analysis indicates that incidence can be predicted largely by considering only the previous history of incidence in the county—the inclusion of climate- or weather-related time sequences improves the model only to a relatively minor extent. Our work therefore suggests that incidence fluctuations (about a seasonally varying background value) are related to biological and/or anthropogenic reasons, and not so much to weather or climate anomalies