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

BMC Microbiology

Christopher H Woelk³  Theo N Kirkland⁴  Jonathan Goldberg²  Joshua Fierer⁴  Akul Singhania³  Suganya Viriyakosol¹ 

[1] Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA;The Broad Institute, Cambridge, MA 02142, USA;Research Service, Veterans Affairs San Diego Healthcare System(111F), 3350 La Jolla Village Dr, San Diego, CA 92161, USA;Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA

关键词: Transcriptome;    Gene expression;    Mycelia;    Spherules;    Fungus;    Coccidioides;   

Others  :  1143686
DOI  :  10.1186/1471-2180-13-121

 received in 2013-01-14, accepted in 2013-05-20,  发布年份 2013

【 摘 要 】

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 α (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.

【 授权许可】

   
2013 Viriyakosol et al.; licensee BioMed Central Ltd.

【 图 表 】

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