Oral Presentation MedVetPATHOGENS 2018

Characterisation and engineering potential of an Actinobacillus pleuropneumoniae glycosyltransferase  (#49)

Jon Cuccui 1 , Vanessa Terra 1 , Janine Bosse 2 , Ian Passmore 1 , Andreas Nageli 3 , Sherif Abouelhadid 1 , Yanwen Li 2 , Lin Chia-Wei 3 , Prerna Vohra 1 , Dan Tucker 4 , Andrew Rycroft 5 , Duncan Maskell 4 , Markus Aebi 3 , Paul Langford 2 , Brendan Wren 1
  1. London School of Hygiene and Tropical Medicine, London, LONDON, United Kingdom
  2. Imperial College, London
  3. ETH, Zurich
  4. Univeristy of Cambridge , Cambridge
  5. RVC, London

Actinobacillus pleuropneumoniae is a mucosal respiratory pathogen that can glycosylate proteins, using a cytoplasmic N-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. We investigated the NGT locus and demonstrated that the putative transcriptional unit consists of rimO, ngt and a glycosyltransferase termed agt. From this information we used the A. pleuropneumoniae glycosylation locus to decorate an acceptor protein, within Escherichia coli, with a hexose polymer that reacted with an anti-dextran antibody. Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. The enzyme has significant biotechnological potential, and several groups, including ours, are now working to exploit it as a glycoenengineering tool.