Research in Focus: Investigating Teixobactin

As part of #BiofilmWeek, we’re highlighting interesting and exciting biofilm research from across our network and partner research institutions by early career researchers and PhD students.

We interviewed Teresa To, a PhD student at the University of Liverpool. Teresa’s work focuses on the development of new classes of antibiotics and antibiofilm agents, which can be potentially used in clinic to treat bacterial and biofilm infections.

 

How does your work link to biofilms and Antimicrobial resistance (AMR)?

My work primarily focuses on developing new analogues of the antimicrobial peptide (AMP) teixobactin and evaluate their biological activities against Gram-positive bacteria and biofilms. We aim to address AMR by introducing new classes of antibiotics into the drug pipeline in the hope of saving patients’ lives when other treatment options do not work, which are mainly caused by the presence of multidrug resistant bacteria.

My project further investigates the antibiofilm properties of teixobactin analogues against Gram-positive bacterial biofilms. Currently, there are no marketed treatments to treat biofilm infections and combinational therapy involving conventional antibiotics is used. There is a need for new potential treatments which target biofilms in healthcare settings.

 

What problems do you hope to address through your work?

My work aims to address the lack of approved treatments for bacterial and biofilm infections. There are decreasing numbers of approved antibiotics in the market and most of them are based on the modifications of existing classes of antibiotics. On the other hand, the number of resistant bacterial strains is increasing at an alarming rate. Therefore, new classes of antibiotics are in need to address the AMR issue.

The other part of my work hopes to target biofilms in clinical treatments. The presence of bacterial biofilms in tissue or medical implants makes treatment difficult because of high risk of reinfection and high resistance/tolerance rate of sessile cells in biofilms. This project is more of a proof of concept to test if teixobactin analogues or other antibiofilm agents are able to inhibit biofilm formation or disrupt preformed biofilms. We hope to find some lead compounds which can be further tested for antibiofilm activity both in vitro and in vivo.

Are there any highlights/discoveries from your work you can tell us about?

Previous research from our group has shown an efficient synthesis of teixobactin analogues with higher yields and also show similar/even higher potency compared to the natural product. We propose that this is ideal for library generation and potential drug development.

Recently we published our latest work on teixobactin analogues containing hydrophobic, non-proteogenic amino acids in which we found that the analogues are highly potent against multidrug-resistant Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). In this study, we also performed the first antibiofilm study of teixobactin analogues against pre-formed biofilms of Staphylococcus species where teixobactin analogues show certain levels of biofilm disruptions as shown from dead/alive cell ratio compared to positive control. We believe that this study allows us to investigate further into the antibiofilm properties of teixobactin analogues in addition to possible synergies when antibiofilm agents are applied.

Have you undertaken any public engagement and outreach activities?

I had the opportunity to volunteer as a demonstrator for science outreach events when I was an undergraduate student at University of Southampton, where I helped school students with science experiments and show the day-to-day life as a scientist. I also answered questions regarding the life of a university student and how to choose a subject of interest in a course. NBIC has promoted many outreach activities and I hope to volunteer if I have the chance to do so.

How has NBIC supported you with in your career?

The NBIC Biofilms Innovation, Technology and Engineering (BITE) studentship has supported the funding of my PhD programme, making all the exciting research possible. NBIC has provided many opportunities such as courses, outreach and summits to gain new knowledge of biofilm studies and meet the experts from NBIC community. Some particular examples are the BITE-Collaborative Training Programme (CTP) courses in Nottingham and Southampton, which involve microbiology, imaging, models and omics techniques to study biofilms. I have learnt a lot of new techniques to study biofilms and I am very grateful to meet all the biofilm experts from NBIC community.

One particular example is the training I have received when I worked with my third supervisor’s group when I was trained on antimicrobial pharmacology and microbiology. I was able to learn valuable techniques to test antimicrobial activity of our analogues such as MIC, time-kill kinetics and resistance studies. In terms of biofilm studies, after the Nottingham BITE-CTP, I reached out to Professor Miguel Cámara’s group regarding biofilm assays and Dr. Shaun Robertson provided some protocol example and advice which helped me to design my own biofilm assay protocols to test our teixobactin analogues. I am very grateful for NBIC to provide all the opportunities to do all the research for my PhD project and the networking to further improve many aspects of my research to gain new skill sets.

Find out more

If you are interested in learning more about this work and would like to connect with Teresa please contact NBIC at nbic@biofilms.ac.uk.

 

Teresa To, PhD Student at the University of Liverpool.

NBIC Jasmine