GliA in Aspergillus fumigatus is required for its tolerance to gliotoxin and affects the amount of extracellular and intracellular gliotoxin.
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.
Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Dan-Ni
DN
Wang
Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11 Inada-cho, Obihiro City, Hokkaido 080-8555, Japan tome@obihiro.ac.jp.
Takahito
T
Toyotome
Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Yasunori
Y
Muraosa
Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan Division of Control and Treatment of Infectious Diseases, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677, Japan.
Akira
A
Watanabe
Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Tuya
T
Wuren
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Somnuk
S
Bunsupa
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Kaori
K
Aoyagi
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan.
Mami
M
Yamazaki
Japan Application Center, Life Sciences and Chemical Analysis, Agilent Technologies Japan, Ltd., Hachioji Site, 9-1, Takakura-cho, Hachioji City, Tokyo 192-8510, Japan.
Masahiko
M
Takino
Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8673, Japan Division of Control and Treatment of Infectious Diseases, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677, Japan.
Katsuhiko
K
Kamei
D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D002460:Cell Line; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005912:Gliotoxin / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014774:Virulence; D037521:Virulence Factors
D005656:Fungal Proteins; D037521:Virulence Factors; D005912:Gliotoxin; C552832:GliT protein, Aspergillus fumigatus; D010088:Oxidoreductases
Aspergillus fumigatus; GliA; gliotoxin; major facilitator superfamily transporter