The Trehalose Pathway is critical for Aspergillus fumigatus virulence

Srisombat Puttikamonkul*, Sven D. Willger, and Robert A. Cramer Jr.

Author address: 

Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT, USA.

Abstract: 

Trehalose, a disaccharide sugar, accumulates in Aspergillus conidia and plays a role in protection against stress including: high temperature, high osmolarity and ROS. In this study, we have characterized the trehalose pathway in A. fumigatus for the first time. Phylogenetic analyses revealed multiple copies of the trehalose biosynthesis gene tps1 (tpsA and tpsB), a single copy of the trehalose-6-phosphate (T6P) phosphatase tps2 (orlA), and single copies of tps3 and tsl1 orthologs. W e have generated single and double null mutants of tpsA and tpsB and show that both genes are required for trehalose biosynthesis. Generation of a single tpsA or tpsB mutant did not alter trehalose accumulation, while generation of a tpsA tbsB double mutant completely abolished trehalose biosynthesis. Generation of an orlA (tps2) null mutant revealed a role for orlA in asexual conidiation when cultured on glucose minimal media. However, the defect in conidiation could be recovered on both sorbitol and glycerol minimal media. The orlA and tpsA tpsB mutants displayed sensitivity to growth at high temperatures (50 oC). Surprisingly, lack of orlA did not affect the production of trehalose at 37 oC suggesting an alternate pathway for trehalose biosynthesis exists in A. fumigatus. Of particular interest, the orlA null mutant was avirulent in two murine models of invasive aspergillosis. Our results suggest that trehalose and T6P are important components of the biology of A. fumigatus. Importantly, our results suggest that T6P phosphatase contributes to the ability of this mold to cause lethal disease in immunocompromised patients. Thus, as others have suggested, the trehalose pathway is worth exploiting as an antifungal drug target given its conservation in other pathogenic fungi and absence in humans. *Student poster
2009

abstract No: 

51

Full conference title: 

6th International Aspergillus Meeting
    • Asperfest 6 (2009)