antimicrobial resistance citizen science clinical microbiology publication research tuberculosis

New publication: BashTheBug works!

Yesterday eLife published the first paper from our citizen science project, BashTheBug, which was launched in April 2017 on the Zooniverse platform. Through BashTheBug we asked for volunteers to classify images of M. tuberculosis growing on a range of concentrations of 13 different antibiotics. The images were derived from photographs of 96-well plates taken after […]

antimicrobial resistance research tuberculosis

New publication: WHO catalogue of Mycobacterium tuberculosis resistant mutations

The CRyPTIC project collecting over 20,000 clinical samples of TB and for each, sequencing its genome and testing its susceptibility to 13 different antibiotics. A lovely unintended consequence of compiling such a large high-quality dataset is that CRyPTIC was invited to form part of the team that collected data and compiled the first catalogue of […]

antimicrobial resistance clinical microbiology computing group molecular dynamics publication research tuberculosis

New preprint: Predicting antibiotic resistance in complex protein targets

In this preprint, which Alice has been working on for several years, we show how alchemical free energy methods can predict whether an amino acid mutation confers resistance to an antitubercular, but only in cases where the change in binding free energy is large. This is mainly because the confidence limits on the change in […]

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 […]

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 […]

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 […]

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 […]

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 […]

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 […]

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).