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 Successful NIHR grant 29th June 20185th August 2018 Last year I coordinated a bid to the NIHR for capital to improve our research… 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 GARC: A Grammar for Antimicrobial Resistance Catalogues 25th November 201817th November 2020 During the CRyPTIC project it has become obvious that we need a grammar to describe… 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 BashTheBug.net Beta Testing Results 5th April 20175th August 2018 Zooniverse have finished beta-testing my BashTheBug citizen science project. To verify that the task is… 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