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PLoS Genet DOI:10.1371/journal.pgen.1005493

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

Publication TypeJournal Article
Year of Publication2015
AuthorsMuñoz, JF, Gauthier, GM, Desjardins, CA, Gallo, JE, Holder, J, Sullivan, TD, Marty, AJ, Carmen, JC, Chen, Z, Ding, L, Gujja, S, Magrini, V, Misas, E, Mitreva, M, Priest, M, Saif, S, Whiston, EA, Young, S, Zeng, Q, Goldman, WE, Mardis, ER, Taylor, JW, McEwen, JG, Clay, OK, Klein, BS, Cuomo, CA
JournalPLoS Genet
Volume11
Issue10
Pagese1005493
Date Published2015 Oct
ISSN1553-7404
KeywordsAnimals, Blastomyces, Blastomycosis, Chrysosporium, Genome, Fungal, Histoplasmosis, Humans, Macrophages, Mice, Paracoccidioidomycosis, Transcriptome
Abstract

Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution and of factors contributing to virulence in Blastomyces.

DOI10.1371/journal.pgen.1005493
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26439490?dopt=Abstract

Alternate JournalPLoS Genet.
PubMed ID26439490
PubMed Central IDPMC4595289
Grant List1R21AI105537 / AI / NIAID NIH HHS / United States
5K08AI071004 / AI / NIAID NIH HHS / United States
AI040996 / AI / NIAID NIH HHS / United States
AI093553 / AI / NIAID NIH HHS / United States
HHSN272200900018C / AI / NIAID NIH HHS / United States
R01 AI035681 / AI / NIAID NIH HHS / United States
R01 AI035681 / AI / NIAID NIH HHS / United States
R21 AI105537 / AI / NIAID NIH HHS / United States
T32 AI055397 / AI / NIAID NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States