| Trehalose is a non-reducing dissacharide of glucose involved in the metabolism of bacteria, plants, insects and fungi that is not present in mammals. In fungi, trehalose serves as source of energy for reproduction and development, and it can protect cells from environmental stress and nutrient limitations. It has also been linked with virulence in pathogenic yeasts. Trehalose biosynthesis in fungi involves a protein complex consisting of trehalose-6-phosphate synthase (Tps), trehalose-6-phosphate phosphatase (Tpp), and regulatory proteins. In the pathogenic mold Aspergillus fumigatus, we located four putative trehalose-6-phosphate synthases: tpsA, tpsB, tpsC, and tpsD. We found that trehalose accumulated during the developmental life cycle of A. fumigatus, throughout which both tpsA and tpsB were significantly expressed. In stress, trehalose accumulated only during heat shock, and this accumulation correlated with an increase in expression of tpsA. We therefore created strains of A. fumigatus in which tpsA, tpsB, or both were disrupted. Only the DeltatpsAB double mutant failed to accumulate trehalose under any conditions. The DeltatpsAB mutant was also delayed in germination at normal growth temperature, suggesting a developmental defect. With heat stress, most DeltatpsAB spores were found to be non-viable, and those that were viable were severely delayed in germination, growth and subsequent sporulation. No clear correlation could be made between DeltatpsAB and susceptibility to oxidative stress; however DeltatpsAB may have an abnormal cell wall. Further studies in mice are underway to determine if the DeltatpsAB mutant is impaired in virulence, potentially making the trehalose synthase complex a promising new target for antifungal therapy. |
