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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+Genet
2015 ; 11
(10
): e1005493
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The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and
Close Relative Emmonsia
#MMPMID26439490
Muñoz 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
PLoS Genet
2015[Oct]; 11
(10
): e1005493
PMID26439490
show ga
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.