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 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.
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).
Original publication:
Target protection as a key antibiotic resistance mechanism (2020) Daniel N. Wilson, Vasili Hauryliuk, Gemma C. Atkinson & Alex J. O’Neill, Nature Reviews Microbiology
You can read the full article here.
About the Atkinson lab and Hauryliuk lab
Gemma C. Atkinson and Vasili Hauryliuk are specialists in microbial protein synthesis, antibiotic resistance and stress responses. The great strength of the two research groups is in their combination of creative and sensitive bioinformatics methods combined with experimental approaches such as structural biology, microbiology, molecular biology and biochemistry.
Contact persons:
Gemma C. Atkinson, associate professor
Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University
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Vasili Hauryliuk, associate professor
The Laboratory for Molecular Infection Medicine Sweden (MIMS)
Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University
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http://www.mims.umu.se/groups/vasili-hauryliuk.html
Figure provided by V. Hauryliuk from the publication Wilson et al. (2020) Target protection as a key antibiotic resistance mechanism. Nature Reviews Microbiology.
