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
antimicrobial resistance New publication: Predicting resistance is (not) futile 21st August 201921st August 2019 Our “First Reactions” article has been published in ACS Central Science. We discuss the paper,… 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
antimicrobial resistance New preprint: Predicting antibiotic resistance in complex protein targets 4th January 20224th January 2022 In this preprint, which Alice has been working on for several years, we show how… 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
antimicrobial resistance New preprint: Predicting pyrazinamide resistance by machine learning 29th April 201929th April 2019 Usually, the protein that an antibiotic binds is essential for bacterial survival, which is how… 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