Antimicrobial resistance is a major threat to modern medicine, reducing our ability to prevent or cure disease.

Antimicrobial resistance on the rise

“I remember when I was a kid, I used to see people taking antibiotics like Septran DS.  It’s vanished from the market in most of the places in the world as there’s so much resistance in bacteria, meaning the treatment is no longer effective,” reflects Yasir.

“E.coli bacteria are now resistant to third generation antibiotics like fluoroquinolones and cephalosporines. We need to find ways to reuse those antibiotics again,” highlights Sajid.

He continues, “My PhD at the University of Copenhagen is working on E.coli and how E.coli has developed resistance to the antibiotics called sulfonamides and trimethoprim. These antibiotics are often used together to treat urinary tract infections.”

“I’m studying the mechanisms of how these antibiotics targets the E.coli, with the aim of to find secondary drug targets for helper drugs that can be taken together with sulfonamides and trimethoprim. The aim is that we can resensitise the E. coli to sulfonamides and trimethoprim by using helper drugs and make these antibiotics effective again.”

“As part of my PhD program, there is a mandatory component known as secondment, which requires me to immerse myself in a different research environment to broaden knowledge and skills relevant to my current project.”

“Since I am investigating the molecular responses of E. coli to sulfonamides and trimethoprim by using TraDIS, I was eager to learn about TraDIS-Xpress, an advanced version of TraDIS. This led me to the Quadram Institute, where I could gain valuable insights into this innovative research approach.”

TraDIS-Xpress training to track down target genes for helper drugs

Here at the Quadram Institute, our researchers developed the TraDIS-Xpress method. The method introduces small pieces of DNA called transposons into bacterial genes to make a mutant library.

The method tests how different transposon mutated genes affect bacterial survive in different conditions. TraDIS-Xpress allows researchers to understand the roles of different genes inside the bacteria and how important the genes are for the bacteria’s survival.

Yasir highlights the difference between TraDIS and TraDIS-xpress, “In TraDIS, we can only investigate the roles of non-essential genes (genes that can be mutated) under stress conditions. However, with TraDIS-Xpress, we can also explore the roles of essential genes (genes that cannot be mutated) during stress. An essential gene is one that a bacteria needs to survive. If this gene isn’t there or switched on, then the bacteria dies.”

“I got an email from Sajid, asking about a placement to learn more about TRADIS-Xpress. We first came in contact as Sajid had a question about data analysis couple of years back and he reached out to me as we often approached by different researchers across globe regarding TraDIS-Xpress” describes Yasir.

He continues, “Luckily our availability matched and Sajid joined us at the Quadram Institute in October 2024 for a six-week placement to learn more about the TraDIS-Xpress method.”

Sajid explains, “Before I came, I had read the paper about TraDIS-Xpress from the Quadram Institute team but I did not understand it fully. Coming here, helped me learned a lot more about the method and how it works in the lab.”

“The method is helpful to my PhD project as I can find which genes are essential under certain sulfonamides and trimethoprim treatment.”

Sajid highlights another strand of research he has carried out at the Quadram Institute, “We have also used phytochemicals to suppress E.coli and see how E. coli survives in the stress of thymol by using TraDIS-Xpress. Thymol is an essential oil that comes from the thyme plant and can be found in over-the-counter antibacterial and antifungal products.”

Sajid’s second PhD

Sajid explains his path to his current second PhD, “I am from Pakistan. I did my undergraduate in my home city at the University of Agriculture, Faisalabad. I studied veterinary studies there for five years.”

“After that I did my masters at the same university in Public Health and Climate Change. Then I continued at the University of Faisalabad and started my PhD in 2018. In Pakistan I was doing a PhD on the bacteria Salmonella Typhi to investigate how S. Typhi survive in varying concentrations of metal ions like iron, copper, manganese and cobalt.”

“In 2021 I got a scholarship from Punjab Education Endowment Fund (PEEF) to start a new PhD in Copenhagen. My supervisor M Imran Arshad suggested having a PhD from University of Copenhagen, Denmark would develop my research career and I could freeze my degree in Pakistan. At the time, I had finished my research and was writing my thesis so it was decided I can submit my thesis for the work I did in Pakistan, when I finish my PhD in Copenhagen.”

Exchanging expertise

Reflecting on his placement at the Quadram Institute Sajid says, “My experience at the Quadram Institute has been nothing short of exceptional. I thoroughly enjoyed my time here, as the facilities are truly state-of-the-art. The atmosphere is vibrant and inspiring, allowing me to engage deeply with my research. I’ve had the opportunity to learn a great deal and have been continuously impressed by the level of expertise and dedication among the staff.”

“During my visit, I gained a comprehensive understanding of the fundamentals of TraDIS-Xpress, including its operational mechanisms and the underlying concepts that drive this innovative technique. This knowledge is highly valuable for my research and will undoubtedly enhance my ability to analyse the survival mechanisms of E. coli in the presence of various compounds.”

“I would like to express my heartfelt gratitude to everyone at the Quadram Institute for their warm welcome and support. The kindness and humility of the staff have made my experience even more enriching. Special thanks to Yasir, who provided valuable assistance throughout my experiments, and to Professor Mark Webber, along with Keith, Ryan, and other group members for their guidance and encouragement. This experience has not only advanced my research skills but also fostered meaningful connections that I will cherish throughout my academic journey.”

Yasir concludes, “It’s been great to have Sajid join us in the Webber group to learn more about TraDIS-Xpress. Our collaboration established by Sajid’s visit is ongoing and we will publish collaborative work together on how we can help tackle antibiotic resistance.”