From bacterial behaviours to COVID-19

Sushmita Sridhar has paused her work on a gastroenteritis-causing bacterium to help diagnose the virus that causes COVID-19. She is part of a team at Addenbrooke’s Hospital in Cambridge which set up an on-site laboratory to rapidly test healthcare workers for the virus. In a report published last month, they showed that of 1,032 healthcare workers without any symptoms, three per cent tested positive for SARS-CoV-2. Their findings have been helping to inform hospital policy and infection control procedures.

Sushmita Sridhar, PhD student in antimicrobial research

What is your day job at Sanger?

I’m a PhD student working on Salmonella Typhimurium, trying to understand how bacteria respond to antimicrobial stress. Questions I’m investigating include: What do bacteria look like, and how does their behaviour change when they’re exposed to antimicrobials, what are their mechanisms of resistance, and what does that mean for appropriate drug use?

Tell us about your COVID-19 work

I’m in Gordon Dougan’s group, which was previously based at the Sanger Institute and is now at Addenbrooke’s Hospital, Stephen Baker’s group at Addenbrooke’s, and I’m also in Nick Thomson’s group at Sanger.  Because we’re on the Addenbrooke’s Campus, and have a good relationship with the hospital, when the coronavirus became a pandemic my supervisors Steve Baker and Gordon Dougan stepped up and offered our lab. Our lab is intended to be a bridge between research and the hospital, and we have the ability to do RNA extractions from swab samples and  run diagnostic q-PCR tests, so the hospital asked us to screen healthcare workers. We optimised and validated an existing in-house method of RNA extractions that wasn’t reliant on kits when they were in short supply, and made sure everything could happen at containment level (CL) 2 to make it safer for everyone involved.

We worked very closely with the Public Health England microbiology lab within Addenbrooke’s and rapidly set up a diagnostic test, and people from PHE taught us how best to do the test in-house.

Why did you become a scientist?

I think it’s really cool to look at the world and ask, “What’s happening?” There’s so much diversity in organisms, and diversity in what makes them tick. Early on I became fascinated by pathogens – these small organisms that have so much power over us. I wondered how they were able to do so much with such small genomes.

Who is your science hero?

Probably Stanley Falkow – he was one of my professors during my undergraduate degree at Stanford. He inspired me to learn more about microbes and microbiology, and to appreciate bacteria. Sadly, he passed away a couple of years ago.

What is the most exciting development in your field from the last 10 years?

The integration of all sorts of technologies has been really powerful. Everyone talks about genomics and sequencing as a really big thing (and it has been revolutionary), but I think the ability to integrate genomic data with transcriptomic data, with phenotypic data that you’ve retrieved from a microscope with microbiological assays, and put those together to get a compendium of knowledge, has been really powerful. The umbrella for that is the ability to work with big datasets, and zoom in and out where you need.

What is the most surprising discovery that you have made?

What I find really intriguing, and this is something that needs to be appreciated more in the field, is that bacteria are actually capable of withstanding much higher concentrations of antimicrobials than we give them credit for. You can treat them with four to eight times the minimum inhibitory concentration of an antimicrobial (a concentration beyond which they shouldn’t be able to grow), and you’ll still get a population that survives. That means we need to be thinking a lot harder in the public health arena about how we treat people with infections, and environmental contamination by antimicrobials.

Another thing I’ve been trying to unravel in my research is the formation of different subpopulations, within an overall population of bacteria. When you treat bacteria with antimicrobials, you end up getting a pretty heterogeneous mixture of bugs that grow. This isn’t ground-breaking, we’ve known this for a while – but I think what warrants a lot more investigation is the differences between these populations, and the importance of these differences when it comes to survival under drug treatment. It could have implications for how we treat people with bacterial diseases.

If you could time travel to any period in history, which would you pick?

I’d be really interested to visit Europe during the Black Death, just to see how people dealt with disease. If I could go with the knowledge I have and be a spectator, that’s what I’d do.

If you were omnipotent for the day, what would you do?

So many things. I think I would put a time limit on how much everyone is able to speak. With how much everything is being politicised right now, we could all benefit from having to listen more. We’d have to appreciate other people’s thoughts and pre-meditate on our actions before taking them.

And I’d plant a billion trees.