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antimicrobial resistance publication research tuberculosis

New Publication: Structure of MmpL3

Oliver Adams successfully elucidated the structure of the M. tuberculosis MmpL3 membrane transporter using cryo-EM and this has recently been published online in Structure. This was the main aim of his PhD studies in Simon Newstead‘s group in the Department of Biochemistry here in Oxford. It is an important protein structure since although other MmpL3 […]

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antimicrobial resistance clinical microbiology computing grants research tuberculosis

Postdoctoral position advertised

Through the CompBioMed2 EU Centre of Excellence project I have funding to appoint a postdoctoral researcher to develop machine-learning models to predict whether an infection is susceptible to an antibiotic. The need for predictive methods, such as these, will grow in the coming years as more of clinical microbiology transitions to using genetics to infer […]

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antimicrobial resistance clinical microbiology publication research tuberculosis

New print: Epidemiological cutoff values for a 96-well broth microdilution plate for M. tuberculosis

In this preprint, the CRyPTIC project proposes the maximum value of minimum inhibitory concentration (MIC) for 13 different anti-TB drugs below which a sample can be considered to be ‘genotypically wild-type’. It is necessary to establish these values, called epidemiological cutoff values (ECOFFs or ECVs), so that the MICs measured can be converted into binary […]

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antimicrobial resistance clinical microbiology computing grants research

Research position advertised

Come and work with me on antimicrobial resistance! Advert here. Broadly the idea is to develop our work using machine learning and molecular simulation to predict whether individual bacterial protein mutations confer resistance to an antibiotic (or not). Any questions please get in touch. For more details please see the advert, especially the lists of […]

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antimicrobial resistance computing distributed computing GPUs molecular dynamics publication research

New publication: how quickly can be calculate the effect of a mutation on an antibiotic?

The idea for this paper arose during talking over coffee at the BioExcel Alchemical Free Energy workshop in May 2019. We’d previously shown that alchemical free energy methods could successfully predict which mutations in S. aureus DHFR  confer resistance to trimethoprim (and crucially, which do not). That is all well and good, but to do […]

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antimicrobial resistance clinical microbiology publication research

New publication: Reconciling the potentially irreconcilable? Genotypic and phenotypic amoxicillin-clavulanate resistance in Escherichia coli.

Clinical microbiology often assumes a sample is resistant or susceptible. Making such a classification relies on applying a threshold (usually called a cutoff) to quantitative data, such as minimum inhibitory concentrations (MICs). If the MICs are strongly bimodal, then this is trivial and reproducibility is guaranteed. If the MICs are unimodal, then one is left […]

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antimicrobial resistance clinical microbiology publication research tuberculosis

New publication: Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex

Although the population structure M. tuberculosis is clonal, one must be careful when inferring the effect of individual mutations on the effect of an antibiotic. Purely because a mutation appears to define a phylogeny does not mean it has no effect on the minimum inhibitory concentration. Read more here (Open Access).

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antimicrobial resistance clinical microbiology computing GPUs molecular dynamics publication research

New preprint: rapid prediction of AMR by free energy methods

The story behind this preprint goes back to the workshop on free energy methods run by BioExcel in Göttingen in May 2019. I gave a talk, based in part on the work I’d previously published showing how alchemical free energy methods are able to predict which mutations in S. aureus DHFR confer resistance to trimethoprim.

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antimicrobial resistance clinical microbiology publication research tuberculosis

New preprint: Predicting pyrazinamide resistance by machine learning

Usually, the protein that an antibiotic binds is essential for bacterial survival, which is how the drug has its effect. In this case, relatively few protein mutations arise that confer resistance, they are often subtle in nature and one can try to predict the phenotype of a protein mutation by considering how it affects the […]

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antimicrobial resistance clinical microbiology grants research

Successful NIHR grant

Last year I coordinated a bid to the NIHR for capital to improve our research capacity to study antimicrobial resistance (AMR) at the Oxford Biomedical Research Centre. We were successful and were awarded £1.8 million to fund several different activities, including developing vaccines to prevent the spread of AMR.   Previously in the John Radcliffe […]