CharisThompson
Charis Thompson is one of the 2026 recipients of Dr Mrytle Pridgeon's scholarship, which is awarded to two postgraduate students working in Medical Sciences. She is a PhD student in Life Sciences.
Charis' project is called 'Investigating non-tuberculosis mycobacteria serine/threonine kinases as targets for antibiotic resistance attenuation'.
She is supervised by Prof David Roper and Dr Freya Harrison.
Project Summary
Cases of pulmonary disease caused by non-tuberculous mycobacteria (NTM-PD), such as Mycobacterium abscessus, are increasingly prevalent globally. Poor host antibiotic tolerance and the pathogens’ intrinsic resistance to most antibiotics limit the efficacy of the complex multidrug regimens currently used in the treatment of NTM-PD. It is therefore imperative that we investigate novel therapeutic strategies for treating NTM infections.
PknB is an essential serine/threonine kinase that is conserved across the Mycobacterium genus. This kinase has a regulatory role in cell wall synthesis and maintenance, including sensing and responding to antibiotic stress. Additionally, the cell wall of M. abscessus consists predominantly of non-canonical 3-3 peptidoglycan crosslinks formed by L,D-transpeptidases, rather than the “normal” 4-3 crosslinks catalysed by penicillin-binding proteins (PBPs). This alternative form of peptidoglycan crosslinking contributes towards beta-lactam resistance in this organism.
This project investigates the role of M. abscessus PknB and its influence on peptidoglycan cell wall synthesis, such as the balance between canonical and beta-lactam resistant crosslinking patterns, and how chemical inhibition of PknB may influence antibiotic sensitivity. We are utilising a combination of biochemical, biophysical, and microbiological approaches to investigate this hypothesis. If correct, repurposing existing kinase inhibitors and administering them in combination with beta-lactams could present novel effective treatment regimens for M. abscessus and associated NTM infections.
