Journal article

A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites

M Fleur Sernee, Julie E Ralton, Tracy L Nero, Lukasz F Sobala, Joachim Kloehn, Marcel A Vieira-Lara, Simon A Cobbold, Lauren Stanton, Douglas EV Pires, Eric Hanssen, Alexandra Males, Tom Ward, Laurence M Bastidas, Phillip L van der Peet, Michael W Parker, David B Ascher, Spencer J Williams, Gideon J Davies, Malcolm J McConville

CELL HOST & MICROBE | CELL PRESS | Published : 2019


Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of ma..

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Awarded by NHMRC

Awarded by Australian Research Council

Awarded by BBSRC

Awarded by ERC

Awarded by Jack Brockhoff Foundation

Funding Acknowledgements

We thank Professor Steve Beverley for the pXG plasmids; Dr. Thomas Ilg for the L. mexicana Dgmp, Dpmi, and Dpmm mutants; and Dr Eleanor Saunders for assistance with GC-MS analyses. MJM and MWP are NHMRC Principal Research and Senior Principal Research Fellows, respectively. GJD is a Royal Society Ken Murray Research Professor. DBA and DEVP are NHMRC (APP1072476) and Endeavour Fellows, respectively. We acknowledge grant support from the NHMRC (APP1100000 to MJM), the Australian Research Council (DP160100597 and DP180101957 to SJW), the BBSRC (BB/M011151/1 to AM) and ERC (ERC-2012-AdG-322942 to LS), the MRC (RCUK-CONFAP Grant to DRP), and the Jack Brockhoff Foundation (JBF 4186 to DBA). We thank Diamond Light Source for access to beamlines I03, I04 and I24 (proposals mx13587 and mx18598) and support from the Victorian Government Operational Infrastructure Support Scheme.