Disruption of the gene encoding the V-ATPase subunit A results in inhibition of normal growth and abolished sporulation in Aspergillus nidulans.
The authors have previously reported on molecular responses of Aspergillus nidulans to bacterial antifungal metabolites, e.g. bafilomycins and the related concanamycins. These compounds are known inhibitors of V-ATPases and cause dramatic effects on mycelial growth and morphology. In Neurospora crassa, studies have shown that disruption of the gene encoding subunit A of the V-ATPase results in morphological changes and reduced growth similar to those observed after addition of concanamycin. This phenotype, and the fact that this mutation confers resistance to concanamycin, suggests that V-ATPase is the main (or only) target for the antibiotics. However, growth inhibition and morphology changes in, for example, A. nidulans and Penicillium roqueforti are more severe, and thus other targets are possible. In this study, the vmaA gene of A. nidulans, encoding the subunit A of V-ATPase, was disrupted by homologous recombination. The resulting vmaA1 mutant strain displayed extremely slow growth and failed to produce asexual spores. Furthermore, an altered morphology similar to that caused by addition of V-ATPase inhibitors, i.e. bafilomycin or concanamycin, was observed, indicating that V-ATPase is the main target for the antibiotics also in A. nidulans. The vmaA1 mutant was not viable at pH values above 7 and was highly sensitive to high Zn(2+) concentrations, in agreement with previous results from studies of Saccharomyces cerevisiae and N. crassa.
Melin
Petter
P
Department of Microbiology, Swedish University of Agricultural Sciences, Box 7025, S-750 07 Uppsala, Sweden.
Schnürer
Johan
J
Department of Microbiology, Swedish University of Agricultural Sciences, Box 7025, S-750 07 Uppsala, Sweden.
Wagner
E Gerhart H
EGH
Institute of Cell and Molecular Biology, Department of Microbiology, Biomedical Center, Uppsala University, Box 596, S-75124 Uppsala, Sweden.
D001233:Aspergillus nidulans / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D001483:Base Sequence; D004271:DNA, Fungal / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005800:Genes, Fungal; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D021122:Protein Subunits; D013172:Spores, Fungal / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D015032:Zinc / Q000494:pharmacology
D004271:DNA, Fungal; D004791:Enzyme Inhibitors; D018942:Macrolides; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases; D015032:Zinc