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 Updating the Grammar for Antimicrobial Resistance Catalogues 18th July 202418th July 2024 This blog updates an old (and now out of date) post describing the grammar we’ve… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to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 grant: Ox4TB 17th March 202517th March 2025 Very pleased to announce that I am a co-investigator on the recently announced Oxford4TB project… 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 publication: how quickly can be calculate the effect of a mutation on an antibiotic? 20th November 202020th November 2020 The idea for this paper arose during talking over coffee at the BioExcel Alchemical Free… 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