RRC ID 46829
Author Wang DN, Toyotome T, Muraosa Y, Watanabe A, Wuren T, Bunsupa S, Aoyagi K, Yamazaki M, Takino M, Kamei K.
Title GliA in Aspergillus fumigatus is required for its tolerance to gliotoxin and affects the amount of extracellular and intracellular gliotoxin.
Journal Med Mycol
Abstract Gliotoxin is an important virulence factor of Aspergillus fumigatus. Although GliA putatively belongs to the major facilitator superfamily in the gliotoxin biosynthesis cluster, its roles remain unclear. To determine the function of GliA, we disrupted gliA in A. fumigatus. gliA disruption increased the susceptibility of A. fumigatus to gliotoxin. The gliT and gliA double-disrupted mutant had even higher susceptibility to gliotoxin than each individual disruptant. The extracellular release of gliotoxin was greatly decreased in the gliA disruptant. Mice infected with the gliA disruptant of A. fumigatus showed higher survival rates than those infected with the parent strain. These results strongly indicate that GliA, in addition to GliT, plays a significant role in the tolerance to gliotoxin and protection from extracellular gliotoxin in A. fumigatus by exporting the toxin. This also allows the fungus to evade the harmful effect of its own gliotoxin production. Moreover, GliA contributes to the virulence of A. fumigatus through gliotoxin secretion.
Volume 52(5)
Pages 506-18
Published 2014-7-1
DOI 10.1093/mmy/myu007
PII myu007
PMID 24847038
MeSH Amino Acid Sequence Animals Aspergillosis / microbiology* Aspergillus fumigatus / drug effects Aspergillus fumigatus / genetics* Aspergillus fumigatus / pathogenicity Aspergillus fumigatus / physiology Cell Line Fungal Proteins / genetics Fungal Proteins / metabolism* Gene Deletion Gliotoxin / metabolism* Humans Immunocompromised Host Male Mice Mice, Inbred BALB C Molecular Sequence Data Multigene Family Mutation Oxidoreductases / genetics Oxidoreductases / metabolism Sequence Alignment Virulence Virulence Factors
IF 2.822
Times Cited 18
Pathogenic microorganisms