The Trehalose Pathway contributes to key virulence attribute production in Aspergillus fumigatus.

Ref ID: 15896

Author:

Srisombat Puttikamonkul1, Sven D.
Willger1, Nora Grahl1, John R. Perfect2, Navid Movahed3, Brian Bothner3, and Robert A

Author address:

Cramer Jr.1* 1Department of Veterinary Molecular Biology,
Montana State University, Bozeman, MT 59718, 2Department of Medicine, Duke University Medical Center, Durham, NC 27713, 3Department of
Chemistry and Biochemistry, Montana State University, B

Full conference title:

26th Fungal Genetics Conference

Date: 15 March 2014

Abstract:

Recently, our studies on OrlA (Trehalose 6 Phosphate (T6P) Phosphatase) in A. fumigatus suggest that increases in T6P levels lead to decreased activity
of hexokinase, abolished asexual reproduction, cell wall defects, and avirulence in murine models of IPA. However, these phenotypes are not due to loss
of trehalose itself since production persists in the absence of OrlA through an unknown mechanism. Moreover, complete loss of T6P and trehalose
production only occurs when 2 genes, TpsA and TpsB, encoding trehalose 6 phosphate synthases, are both deleted. Intriguingly, loss of TpsA but not
TpsB in strain CEA10 results in cell wall defects that affect fungal pathogenesis further supporting a link between trehalose metabolism and cell wall
dynamics in A. fumigatus. Consequently, we hypothesize that the trehalose biosynthesis pathway and its intermediates play key roles in regulating fungal
cell wall biosynthesis by affecting central carbon metabolism of fungi. These affects consequently have significant ramifications for the ability of A.
fumigatus to cause disease. Further genome sequence analysis of the A. fumigatus genome reveals additional uncharacterized genes predicted to encode
proteins likely involved in trehalose biosynthesis and metabolism. Amino acid alignments of these genes suggests that they may play important undefined
roles in regulating trehalose production underscoring the complexity and unknown mechanisms of action of this pathway in A. fumigatus. Therefore, our
results strongly suggest that trehalose biosynthesis and catabolism are important components of Aspergillus biology that directly affect fungal pathogenesis
by as yet undefined mechanisms.

Abstract Number: NULL

Conference Year: 2011

Link to conference website: NULL

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