High profile review publication on antibiotic resistance from the Hauryliuk and Atkinson labs, MIMS

In this review, published in the influential journal Nature Reviews Microbiology, Umeå researchers Vasili Hauryliuk (also affiliated with Tartu University, Estonia) and Gemma C. Atkinson, together with their collaborators Daniel N. Wilson (University of Hamburg, Germany) and Alex J. O’Neill (University of Leeds, UK) discuss an important and increasingly recognised type of antibiotic resistance: antibiotic resistance through target protection.

Antibiotics bind to and corrupt the functioning of crucial elements of bacterial cells, such as the ribosome that synthesises proteins or RNA polymerase that reads genes to generate mRNA. To counter the action of antibiotics, bacteria have evolved numerous dedicated mechanisms of resistance. Commonly, these resistance mechanisms act by either destroying the antibiotic, pumping it out of the cell or permanently modifying the molecular target so it becomes immune to the antibiotic, e.g. by post-translational modification such as methylation.

In this mechanism, dedicated protein resistance factors transiently bind to the target to restore its function. This restoration of the function can be achieved in several ways. The resistance factors can remove the antibiotic either by sterically competing with the drug (type I target protection mechanism) or inducing allosteric changes that result in drug dissociation (type II). Alternatively, the resistance factor can bind to the antibiotic target and restore its function despite the antibiotic remaining bound (type III).

Over the years Vasili Hauryliuk and Gemma Atkinson have uncovered important aspects of target protection mechanisms that protect the ribosome, such as ABC-F ATPases (Murina et al. JMB 2019, Crowe-McAuliffe et al. PNAS 2018, Murina et al. NAR 2018) and TetO GTPases (Li et al. Nature Communications 2013).

You can read the full article on the MIMS website.

The paper, Target protection as a key antibiotic resistance mechanism (2020) Daniel N. Wilson, Vasili Hauryliuk, Gemma C. Atkinson & Alex J. O’Neill, Nature Reviews Microbiology, is available on the Nature.com website