Head of Biological and Pharmacological Sciences at the AMR Centre
"We are locked in an arms race with microbes, and must bring all our best tools to the fight the growing AMR pandemic." - Professor Kat Holt.
A strength of the LSHTM is that is has a truly global presence. As such we have links and access to drug resistant strains of microbes from clinics and communities around the world, collected by researchers and collaborators for further study. We work on both neglected tropical diseases and emerging pathogens, as well as food-borne pathogens, hospital-acquired infections, tuberculosis and malaria.
Bacterial mechanism(s) of resistance have fascinated scientists for generations. Twelve years after the discovery of penicillin in 1928, the first scientific account reporting bacterial resistance to this ‘magic bullet’ was published. The orchestrated gene expression, mutation(s) and defence mechanisms then rapidly became at the heart of microbiology. Pressing questions for scientists include - How does antimicrobial resistance arise? How do our practices influence it? And how can we prevent resistance from spreading?
Research under this pillar seeks to:
- Find better methods of measuring, diagnosing and predicting AMR (including genomic approaches).
- Identify new targets for the next generation of antimicrobials.
- Consider the benefits of a paradigm-shift away from antimicrobials such as exploring benefits of phage therapy.
- Protect against serious multidrug resistant bacterial infection via immunotherapy (either vaccination or developing of monoclonal antibodies).
- Implement the One Health philosophy.
Areas of active research
The Biological and Pharmacological Sciences pillar is able to contribute to several levels of understanding of AMR. Cutting-edge genomic and proteomic techniques have paved the way to monitor resistance at the genome level, and big-data approaches have generated information that directly helps in discovering genetic determinants of resistance.
Through genetic and biochemical studies, we can learn more about specific resistance mechanisms in unprecedented detail. Ultimately, we are able to rationally design and screen novel selective antimicrobials, measure directly whether they are effective, and ensure that they are safe.
We explore the landscape of alternatives to antimicrobials, such as bacteriophages, vaccines, antiseptics and/or monoclonal antibodies. These could provide new frontiers in combating AMR. We also work on improving our available tools in diagnosing AMR at the point of contact, to speed up and lower the cost of this process.
We are one piece of the puzzle; through additional engagement with policy making, public education, and collaboration with industry, the Biological and Pharmacological Sciences at the LSHTM is working to be part of the solution to AMR.
- Publication: Characterization of posttranslationally modified multidrug efflux pumps reveals an unexpected link between glycosylation and antimicrobial resistance.
- Project: Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE)
- Project: Genomic surveillance of Klebsiella for neonatal sepsis vaccine development
- Project: Metagenomic screening for AMR in malnourished children