Skip to 0 minutes and 5 secondsHi. I'm Dr. Christine Boinett. With me today is Dr. Kate Baker who'll be telling us a bit more about the Shigella project you've just undertaken. Hi, Kate. Could you tell us a bit more about yourself? I actually originally trained as a veterinarian, and that was in Australia. And then I moved to the UK to do my PhD in viruses. And I became exposed to genomics in that PhD, and I really decided to follow that. And so I did a postdoctoral fellow position at the Sanger Institute on pathogen genomes, and that's where I really got hooked.

Skip to 0 minutes and 35 secondsAnd so after a few years of being at the Sanger Institute working with large genome collections, I moved to the University of Liverpool where I am now as a Wellcome Trust Research Fellow and where I lead my own microbial genomics group. And what is Shigella, and what disease does it cause? Of course. So Shigella is a highly contagious, diarrheal illness. It actually only takes 10 organisms to cause a Shigella infection in an individual. And it causes the disease shigellosis, which used to be called bacterial dysentery. And it's typical features are severe abdominal cramps, fever, as well as frequent, loose bloody stools. Now epidemiologically, Shigella is typically found as a kind of traditional, diarrheal disease.

Skip to 1 minute and 18 secondsAnd the demographic is largely children under the age of five in low to middle income nations. But actually, in our study, we were looking at a different form of the disease epidemiologically where it transmits sexually among men who have sex with men. And you mentioned the plasmids as well. The key on those plasmids is the antimicrobial resistance genes that they carry because Shigella, like many other pathogens, is becoming highly antimicrobial resistant. In fact, Shigella was named by the World Health Organisation as one of the top 12 pathogens for which we urgently need new antimicrobials. And you talk about antimicrobial resistance. What implications does this have to public health?

Skip to 2 minutes and 1 secondWell, obviously, antimicrobial resistant infections are very serious on an individual patient level. For a given person, this can mean treatment failure, as well as a more severe disease manifestation. And that causes an increase burden for health care systems as well. But in addition to that individual level, particularly in the case of transferable antimicrobial resistance, there's other things that can happen. Epidemiologically, when we have a transferable antimicrobial resistance, it can move into another pathogen. And that's something that we saw happen in our study. When an already transmitting pathogen acquires a new antimicrobial resistance profile, it can trigger a new epidemic. And not only trigger a new epidemic, but it can enhance existing epidemics.

Skip to 2 minutes and 49 secondsThen we can see the case numbers shoot right up. And with this transmissibility, is it something you see happening all the time? Well, the thing with transmissible antimicrobial resistance is that we know that it happens. We know that bacteria can exchange plasmids and other mobile genetic elements that carry antimicrobial resistance. We see evidence for this in the fact that we see the same resistance genes in different pathogens in different countries all around the world. But one unique thing about this study is that what we've been able to do is observe an individual antimicrobial resistance plasmid disseminate really quite rapidly around the world.

Skip to 3 minutes and 27 secondsSo in our initial study, we found a Shigella sub-lineage that had transmitted in an international population of men who have sex with men within 20 years. So starting from the UK, we collaborated with people in France, Australia, and Canada. And we found that the same Shigella sub-lineage was disseminated everywhere. And in the final six years of that time frame, we found that an individual resistance plasmid had been enriched in that lineage across that wide geographical space. And when we compare the plasmids between those different sub-lineages, we see that it's actually an identical plasmid. So to take the example of the United Kingdom, for example, we did quite a focus study.

Skip to 4 minutes and 12 secondsAnd what we found was that there were three separate species of Shigella that were going epidemic. This was actually attributable to nine different sub-lineages of shigella. And out of those nine different sub-lineages, seven of them carried exactly the same antimicrobial resistance plasmid. And we could see evidence that the plasmid was transmitting horizontally between these different epidemic sub-lineages. So you can see here on this slide the epidemiological information we have for the UK context. We had three, independent epidemics of Shigella types going on. And when we looked genomically, We found that that was actually attributable to nine different Shigella sub-lineages. And seven of those nine sub-lineages were all carrying an identical antimicrobial resistance plasmid, pKSR100.

Skip to 5 minutes and 1 secondYou mentioned pKSR100, this is the plasmid the learners we'll be looking at. Could you give us a bit more insight into these plasmids in comparison to R100? Well, actually pKSR100 is very closely related to R100, which is why it was used the base name. But the R100 plasmid has been observed in Shigella since the 1960s. And it carries resistance against a variety of antimicrobials including tetracyclines, aminoglycosides, sulfadimidines, and chloramphenicol. But the key distinction between these plasmids is those resistance profiles, is that actually pKSR100 carries resistance against one of our more modern macrolide antibiotics, azithromycin.

Skip to 5 minutes and 44 secondsAzithromycin is an antibiotic that's really commonly used among the high risk MSM sub-population, the high risk men who have sex with men sub-population that we saw these Shigella outbreaks in. Thanks again, Kate for taking the time to give us a bit more information about the project. It's my pleasure Christine. And I wish the students well on the course.

Interview with Dr. Kate Baker - Discussion of the Shigella project

Dr Kate Baker was interviewed by Dr Christine Boinett about her research, which further explains the peer project you have just undertaken and putting it into context.

You will find a link to the article where Kate and collaborators published the work on the pKSR100 plasmid in Shigella. You can find the published research article here.

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