Oh when you didn't sing the title you were going to oh I've got to do that ah trapped

in an elevator anyone recognize Aerosmith there maybe I'm different generation so my

name is Ren Dobson I've come from the University of Canterbury New Zealand I'm going to actually

follow on from Esther's talk actually where we she introduced the idea of targeting virulence

factors as opposed to antibiotics and I'm going to talk a little bit about how bacteria import

sugars during the process of colonization and pathogenesis and how we might understand that

import in order to block it and the proteins we're going to talk about are trap transporters

hence the name I'm going to start with the acknowledgments and in particular three people

this is James Davies Michael Currie and Rachel North they really started this Rachel North was

the one who really took this project maybe to 2016 I think she didn't really didn't want to

work on membrane proteins but it turned out that this worked out really well there's a big crew of

people who have helped along the way so we've been working on this for probably six years and of

course I also want to acknowledge the funders which are down the bottom but in particular I

want to thank you guys because you're the ones that design the experiments that design right the

software that we use and we really appreciate that and we really couldn't do what I'm going to talk

about today without you so thank you all right so I'm going to talk a little bit about sialic acid

this is the sugar and how that's related to bacterial pathogenesis I'm going to introduce

traps transporters what we knew at the start of the project then I'm going to step through a

series of experiments that we did we're a structural biology lab so there's going to be a

fair bit of structural biology and then we'll end up with the model that we've come up with to try

and explain transport at the end why were we interested in sialic acid metabolism well it turns

out that on our cells they're heavily glycated and there's all sorts of different types of sugars

but the terminal sugar is almost always a sialic acid and so here is a good cell painting on the

outside of the cell of these glycans and they're really described as a forest and then if you break

that forest down they can either be on proteins or they can be on the lipids then on the top here

and these red triangles are the sialic acid so there's actually quite a high concentration of

sialic acid in the environment for bacteria to grow on although most of its locked up on those

cell surfaces so what is sialic acid sometimes called neuraminic acid depending on who you like

two people discovered it at the same time one called it sialic acid one called neuraminic acid

but essentially it's an amino sugar so it's a sugar so it can supply energy it's an amino sugar

which is useful because it can supply nitrogen as well and bacteria like to take up sialic acid

for lots of reasons and actually really for I think key reasons so the first is when they

take it up into the cell they can use it for energy so they can shift the glycan part of

this into glycolysis and make energy they can also some very clever bacteria put those sialic

acids back on their own cell surface and they do that to evade the innate immune system hemophilus

influenza does this the precursors when you break down sialic acid are also used in peptoglycan and

the precursors are also used in capsule formation so there are lots of different parts of the

bacterial cycle where sialic acids are useful just to give you a hint here of how we know that

sialic acids are important for pathogenesis this is streptococcus pneumoniae which is a really

tricky pathogen to work with it's generally commensal but often when it's pathogenic it can

be a real problem and so here's some poor mice have been infected with streptococcus pneumoniae

if you supply a little bit of sialic acid you get an increase in the nasal cavity of growth but one

thing that happens is if you look at these poor mice lungs I guess you kill the mice and then you

look at what's in the lungs you find that the bacteria will now be colonizing and pathogenic

in the lungs of the mice but that only happens if you supply sialic acid these other molecules are

also amino sugars this one down here is just to demonstrate that if you have sialic acid around

streptococcus pneumoniae can form biofilms if you don't it can't all right so it's important this

is not the only organism it's important for and so they really spurred us to start looking at

sialic acid metabolism in bacteria turns out if you look for the genes for the breakdown of sialic

acid you only find it in bacteria well you almost only find it in bacteria that colonize