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Much of the recent work in the laboratory has focused on the role of the important host derived sugar molecule sialic acid. Sialic acid is 9-carbon sugar that is present as the terminal glycosyl motif on a large number of human glycoproteins, lipds and gangliosides.
As a result bacterial pathogens have co-opted sialic acid for several purposes that include providing nutrition, a site of adhesion, a means to modulate the host immune system and as a molecule for host mimicry via glycosylation of bacterial LPS, capsule or protein.
Sialic acid transport and harvesting
Sialic acid transport and harvesting
Our work on Tannerella forsythia identified not only that this fastidious anaerobic pathogen could use sialic acid as a growth factor but also the prototype member of a new family of sialic acid transporters in bacteria (Roy et al., 2010).
We are currently investigating the molecular mechanisms and function of the proteins in this transport system alongside the various scavenging enzymes present in this family of bacteria. (see schematic and structure of binding protein below)
Model of Sialic acid uptake in Tannerella
Structural model of NanU sialic acid binding protein
Role of sialidases in pathogenesis, physiology and microbial communities
Role of sialidases in pathogenesis, physiology and microbial communities
Several periodontal pathogens produce sialidase enzymes that are capable of the cleavage of glycosidic linkages between sialic acid and sub-terminal sugars such as galactose or glucose.
We have shown that for Tannerella forsythia and Porphyromonas gingivalis that these are key to growth on model sialloconjugate sugars in Biofilm models (Frey et al.) and can harvest sialic acid from human cells (below).
In collaboration with Professor Ashu Sharma we have also highlighted that these have a role in interaction with host cells and potentially influence innate immune responses- this is the subject of Galleh’s PhD.
We are also working closely with the Oral Healthcare team at GSK to investigate potential new treatments for periodontal biofilms in this area- with a PhD study (Kitty Ansbro) on the dynamics of microbial communities in relation to glycobiology. We are working hard to produce in vitro multi-species biofilm models (see below).
SEM of mixed species anaerobic in vitro oral biofilm model on HA-MBEC pegs
A previous study (with Ludger Ltd ) on the structural biology and biochemistry of the Tannerella sialidase NanH also revealed several novel aspects of the structure of this enzyme, including a novel CBM (Frey et al.) that we now using as part of in silico studies for drug discovery (Xi Chen, UCSD and Horacio Perez, UCAM)- paper(s) to follow.
We also identified a novel sialate-esterase that is now licensed to Ludger as part of their glycoprofiling portfolio.
Collaborators in this area:
Professor Xi Chen, UCSD
Professor Horacio Perez, UCAM
There are often PhD projects in this area, more details on our Opportunities page.
We welcome enquiries for fellowship projects from talented individuals.
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