Skip to 0 minutes and 5 secondsI'd like to welcome Dr. Alison Mather from the Quadram Institute in Norwich. Alison is going to tell us about the ways in which she has used comparative genomics in her research. Hi, Alison. Hi, Martin. Could you tell us a little about your work? My background is in epidemiology and in microbial genomics. One of the great things over the last few years is with the decreasing cost of genome sequencing and the fact that a lot of the genome data or all of the genome data are open and available to access to anyone, we are able to look at the variation in genomes across different bacterial populations.

Skip to 0 minutes and 39 secondsSo, in my research, what I do is I study the evolution, the antimicrobial resistance, and the transmission of bacteria in a One Health framework. And what that means is recognising that animal health, human health, and environmental health are all interlinked. Please tell us about a piece of your research in which ACT has been important. Sure. I've used ACT in lots of different aspects of my research. So, I've used it to look at how bacteria have evolved over time or how they've changed in response to a selective pressure, such as the use of antibiotics.

Skip to 1 minute and 7 secondsBut what I'm going to tell you about now is a piece of work that I did with some collaborators looking at a certain subtype of Vibrio cholerae in Bangladesh. Tell us a little bit more about Vibrio cholerae. Vibrio cholerae is a bacterium that causes the disease cholera. It is an acute, life-threatening diarrheal disease, which is caught by consuming contaminated water or food. And although many people think it's an ancient disease, it's actually still present today and causing a lot of trouble. It is present in over 40 countries. And every year, tens of thousands of people die from the disease. There are many different kinds of cholera. There's over 200 serogroups, or subtypes, of cholera.

Skip to 1 minute and 46 secondsBut of these, there's only two, which are O1 and O139, which cause the actual disease cholera. In Bangladesh, most of the cases of cholera are caused by the O1 type. However, in 1992 and '93 and in 2002, there were outbreaks of cholera that were caused by the other type, O139. Since 2002, the number of cases of O139 cholera has been only sporadic in Bangladesh, either in clinical cases or in environmental isolates. However, in 2013 and 2014, ongoing surveillance programmes in Bangladesh identified more cases of O139 cholera. These came from both patients that had the disease and also from family members with asymptomatic infection.

Skip to 2 minutes and 34 secondsWhat we wanted to do in this study was to look at the new cases of O139, compare them with previous O139 isolates from previous epidemics in Bangladesh and in other parts of the world, and identify whether it's a new variant of O139 that was in Bangladesh or if the previous variant of O139 had persisted in this area. So, what did you find from this research? So, what we found was using the traditional phenotyping methods, the four isolates were all O139. However, when we looked at the whole genome sequence data, we found a very different story.

Skip to 3 minutes and 4 secondsWhat we found was that three of the four isolates were very genetically similar to the previously identified O139 isolates from Bangladesh and from other parts of the world. However, there was one isolate that was very different. This isolate, even though it was identified phenotypically as an O139 isolate was tens of thousands of SNPs different from the other cholera isolates. So, what you can see on this screen here is a phylogenetic tree showing how the isolates are genetically related to each other. What we have in this tree are both O1 isolates at the top, and then the O139 isolates are at the bottom. The previously characterised O139 isolates are in green.

Skip to 3 minutes and 43 secondsAnd you can see that there are three isolates at the bottom, which are in blue, which represent three of the four cases of cholera from Bangladesh in this period. And you can see that these three isolates of O139 cholera from Bangladesh grouped together with the previously characterised O139 isolates from other parts of the world. So, what's the importance of your findings? We looked at the lipopolysaccharide region of the genomes. Now the lipopolysaccharide region, or the LPS region, is responsible for eliciting an immune response in the host. So, that's for the human body to recognise the bacterium and to cause an immune reaction.

Skip to 4 minutes and 19 secondsAnd what we found was that there is portions of the O139 LPS region that had been transferred into the different genetic backgrounds of this other unusual isolate that we were looking at. Well, that's really interesting. How has whole genome sequencing helped us explore this? So, we use ACT to compare this LPS region between the sequenced isolates, both from this study and from those that have been previously sequenced. And what we found was that even though this unusual isolate had a very divergent genetic background, parts of the LPS region had been transferred into that isolate. And that was enough for it to be identified both phenotypically and by some of the other tests as an O139.

Skip to 4 minutes and 58 secondsThis is also the region that is responsible for determining the serogroup of the Vibrio cholerae. So that's why in our previous tests, it come up as an O139, even though genetically it was very different. So, why is this important to the field of bacterial genomics? In terms of the biology, what we found is that for the most part, the more recent O139 strains that are circulating in Bangladesh are similar to those that had been in previous epidemics. So, it was a persistence of the strains that had been there previously not importation of an entirely new strain. In terms of vaccine coverage, this is really important. Thank you, Alison. That's been really illuminating.

Interview with Dr Alison Mather

In this step, you will watch an interview with Dr Alison Mather

Dr Alison Mather was interviewed by Martin Aslett about her research. Alison will show some of the applications of ACT to her questions about Vibrio cholerae outbreaks.

In the video you will find a link to the article where Alison and collaborators published the work on the outbreak of V .cholerae in Bangladesh. For more information, you can find the published research article on the science discussed here.

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Bacterial Genomes: Comparative Genomics using Artemis Comparison Tool (ACT)

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