Diamond Publications - Search Results

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
I02-Macromolecular Crystallography	Identification of a small molecule with activity against drug-resistant and persistent tuberculosis Feng Wang , Dhinakaran Sambandan , Rajkumar Halder , Jianing Wang , Sarah M. Batt , Brian Weinrick , Insha Ahmad , Pengyu Yang , Yong Zhang , John Kim , Morad Hassani , Stanislav Huszar , Claudia Trefzer , Zhenkun Ma , Takushi Kaneko , Khisi E. Mdluli , Scott Franzblau , Arnab K. Chatterjee , Kai Johnsson , Katarina Mikusova , Gurdyal S. Besra , Klaus Futterer , Scott H. Robbins , S. Whitney Barnes , John R. Walker , William R. Jacobs , Peter G. Schultz Proceedings Of The National Academy Of Sciences 110 (27), E2510 - E2517 DOI: 10.1073/pnas.1309171110 PMID: 23776209 Diamond Proposal Number(s): [6388] Show Abstract ▼ Abstract: A cell-based phenotypic screen for inhibitors of biofilm formation in mycobacteria identified the small molecule TCA1, which has bactericidal activity against both drug-susceptible and -resistant Mycobacterium tuberculosis (Mtb) and sterilizes Mtb in vitro combined with rifampicin or isoniazid. In addition, TCA1 has bactericidal activity against nonreplicating Mtb in vitro and is efficacious in acute and chronic Mtb infection mouse models both alone and combined with rifampicin or isoniazid. Transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb persistence. Genetic and affinity-based methods identified decaprenyl-phosphoryl-β-D-ribofuranose oxidoreductase DprE1 and MoeW, enzymes involved in cell wall and molybdenum cofactor biosynthesis, respectively, as targets responsible for the activity of TCA1. These in vitro and in vivo results indicate that this compound functions by a unique mechanism and suggest that TCA1 may lead to the development of a class of antituberculosis agents.	Jul 2013

Instruments / Technical Area

Publication Details

Published

Actions

I02-Macromolecular Crystallography

Identification of a small molecule with activity against drug-resistant and persistent tuberculosis