Yeast Transcriptome and In Vivo Hypoxia Detection Reveals Histoplasma capsulatum Response to Low Oxygen Tension

Although there is growing understanding of the microenvironmental conditions fungal pathogens encounter as they colonize their host, nothing is known about Histoplasma capsulatum's response to hypoxia. Here we characterized hypoxia during murine histoplasmosis using an in vivo hypoxia detection...

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Bibliographic Details
Published in:Medical mycology (Oxford) 2016-01, Vol.54 (1), p.40-58
Main Authors: DuBois, Juwen C., Pasula, Rajamouli, Dade, Jessica E., Smulian, A. George
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Gene Expression Profiling
Gene Expression Regulation, Fungal
Genes, Fungal
High-Throughput Nucleotide Sequencing
Histoplasma - genetics
Histoplasma - metabolism
Histoplasma capsulatum
Histoplasmosis - microbiology
Histoplasmosis - pathology
Hypoxia
Liver - pathology
Male
Mice, Inbred C57BL
Oxygen - metabolism
Regulon
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Summary:Although there is growing understanding of the microenvironmental conditions fungal pathogens encounter as they colonize their host, nothing is known about Histoplasma capsulatum's response to hypoxia. Here we characterized hypoxia during murine histoplasmosis using an in vivo hypoxia detection agent, Hypoxyprobe-2 (HP-2); and analyzed H. capsulatum's transcriptional profile in response to in vitro hypoxia. Immunohistopathology and flow cytometry analyses revealed distinct regions of hypoxia during infection. Granuloma cells, enriched with macrophages and T-cells isolated from infected livers were 66–76% positive for HP-2, of which, 95% of macrophages and 55% of T-cells were hypoxic. Although inhibited, H. capsulatum was able to survive under in vitro hypoxic conditions (
ISSN:1369-3786
1460-2709
DOI:10.1093/mmy/myv073