Sulphite efflux pumps in Aspergillus fumigatus and dermatophytes.
Dermatophytes and other filamentous fungi excrete sulphite as a reducing agent during keratin degradation. In the presence of sulphite, cystine in keratin is directly cleaved to cysteine and S-sulphocysteine, and thereby, reduced proteins become accessible to hydrolysis by a variety of secreted endo- and exoproteases. A gene encoding a sulphite transporter in Aspergillus fumigatus (AfuSSU1), and orthologues in the dermatophytes Trichophyton rubrum and Arthroderma benhamiae (TruSSU1 and AbeSSU1, respectively), were identified by functional expression in Saccharomyces cerevisiae. Like the S. cerevisiae sulphite efflux pump Ssu1p, AfuSsu1p, TruSsu1p and AbeSsu1p belong to the tellurite-resistance/dicarboxylate transporter (TDT) family which includes the Escherichia coli tellurite transporter TehAp and the Schizosaccharomyces pombe malate transporter Mae1p. Seven genes in the A. fumigatus genome encode transporters of the TDT family. However, gene disruption of AfuSSU1 and of the two more closely related paralogues revealed that only AfuSSU1 encodes a sulphite efflux pump. TruSsulp and AbeSsulp are believed to be the first members of the TDT family identified in dermatophytes. The relatively high expression of TruSSU1 and AbeSSU1 in dermatophytes compared to that of AfuSSU1 in A. fumigatus likely reflects a property of dermatophytes which renders these fungi pathogenic. Sulphite transporters could be a new target for antifungal drugs in dermatology, since proteolytic digestion of hard keratin would not be possible without prior reduction of disulphide bridges.
Léchenne
Barbara
B
Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Reichard
Utz
U
Department of Medical Microbiology and National Reference Center for Systemic Mycoses, University Hospital of Göttingen, Germany.
Zaugg
Christophe
C
Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Fratti
Marina
M
Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Kunert
Jiri
J
Department of Biology, Faculty of Medicine, Olomouc, Czech Republic.
Boulat
Olivier
O
Clinical Chemistry Laboratory, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Monod
Michel
M
Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D003883:Arthrodermataceae / Q000235:genetics / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D003001:Cloning, Molecular; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D025141:Drug Resistance, Fungal; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D008969:Molecular Sequence Data; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013447:Sulfites / Q000378:metabolism* / Q000494:pharmacology; D014249:Trichophyton / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D004271:DNA, Fungal; D013447:Sulfites