Interview with Sushmita Sridhar

Hi I’m Dr. Christine Boinett. I’m here today with Sushmita Sridhar, who’ll be telling us more about her PhD project. Hi Sushmita, could you tell us more about your PhD project and how you use ACT in your studies. I’m a third-year student at the Wellcome Sanger Institute, and Department Of Medicine at the University of Cambridge. And I’m studying ciprofloxacin and resistance and Salmonella Typhimurium. And why is it important to study ciprofloxacin in resistance in Salmonella Typhimurium? So, we’re starting to see an increase in ciprofloxacin resistance in Salmonella Typhimurium. And as I’m sure we’re all aware, AMR, so antimicrobial resistance, is a real problem these days. And ciprofloxacin is currently one of the most widely used antimicrobials to treat invasive Salmonella disease.

And so we’re starting to see an increase in resistance meaning these bugs are able to evade this drug, and we need to come up with alternative scenarios. The truth is that we don’t actually have a very nuanced understanding of how bacteria respond to ciprofloxacin. And what techniques do you use to study the differences in ciprofloxacin resistance in Salmonella Typhimurium? So, most of my techniques are wet lab based. And what I’m doing is I’m collecting a set of Typhimurium isolates from a more global collection to try to compare isolates that have different levels of ciprofloxacin resistance, and potentially different mechanisms of ciprofloxacin resistance.

And in the first instance what I’m doing is growing these bacteria in the presence of ciprofloxacin and measuring growth rate, and how they respond to ciprofloxacin. And then I’m also tying that in with some transcriptomic analysis, also some genomic analysis, to identify differences that might be responsible for ciprofloxacin resistance. You mention looking at multiple strains. How will you use comparative genomics to compare between strains, to answer your research question? Right. So these are all Typhimurium strains, which means that by and large, they’re relatively similar. But there are some differences, obviously, between them.

And so what I would like to do is sort of zoom in on the parts of the genome that are relevant to ciprofloxacin resistance, potentially, and see what changes there might be between them. And see if those differences are, in fact, responsible for the different levels of ciprofloxacin resistance that we see in the lab. As someone just starting out to use ACT, do you have any tips for new learners? I think one of the cool things is that you can look at and compare multiple genomes at the same time. And as I said, I’m interested in looking at a set of isolates. So I have seven to eight isolates at the moment.

And so being able to simultaneously interrogate these genomes is very powerful. Thanks again for joining us, Sushmita, and good luck in your studies. Thank you. It’s been a pleasure.