New preprint: Deciphering bedaquiline and clofazimine resistance in tuberculosis Philip Fowler, 22nd March 202122nd March 2021 In this preprint we examine 14,151 clinical isolates drawn from the CRyPTIC dataset. Each isolate had its minimum inhibitory concentration (MIC) to bedaquiline and clofazimine measured and hence we were able to identify the transcription regulator Rv0678, as the current main source of elevated MICs to both these drugs. Lindsay Sonnenkalb, who is studying for her PhD with Stefan Niemann, then evolved Mycobacterium tuberculosis strains under sub-lethal concentrations of both compounds and was able to identify 189 different Rv0678 genetic variants that confer elevated MICs to bedaquiline and clofazimine. Detailed modelling of the protein structure allowed us to posit four main resistance mechanisms: impairment of DNA binding, reduction in protein stability, disruption of protein dimerization, and reduction in affinity for its fatty acid ligand. Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Related antimicrobial resistance clinical microbiology publication
publication New Publication: Energetics of Multi-Ion Conduction Pathways in Potassium Ion Channels 31st October 2013 Can we predict the conductance of a potassium ion channel from an experimental structure? In this… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Read More
New publication: Predicting antibiotic resistance in complex protein targets using alchemical free energy methods 26th August 202224th October 2022 In this paper, Alice Brankin calculates how different mutations in the DNA gyrase affect the… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Read More
publication New publication: Nothing to Sneeze At – A Dynamic and Integrative Computational Model of an Influenza A Virion 6th March 2015 In this paper we show how we built and then simulated a model of the… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Read More