Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria
Vinayak Singh, Neeraj Dhar, János Pató, Gaëlle S. Kolly, Jana Korduláková, Martin Forbak, Joanna C. Evans, Rita Székely, Jan Rybniker, Zuzana Palčeková, Júlia Zemanová, Isabella Santi, François Signorino-Gelo, Liliana Rodrigues, Anthony Vocat, Adrian S. Covarrubias, Monica G. Rengifo, Kai Johnsson, Sherry Mowbray, Joseph Buechler, Vincent Delorme, Priscille Brodin, Graham W. Knott, José A. Aínsa, Digby F. Warner, György Kéri, Katarína Mikušová, John D. McKinney, Stewart T. Cole, Valerie Mizrahi and Ruben C. Hartkoorn
Version of Record online: 29 OCT 2016 | DOI: 10.1111/mmi.13535
Here a potent anti-tuberculosis compound is described (APYS1), with resistant isolates carrying clustered mutations in the elongation scaffolding protein: Wag31. Visualisation of the impact of APYS1 on Mycobacterium tuberculosisby microscopy reveals gross malformations of the bacterial pole, a phenomenon similar to that observedupon genetic downregulation of wag31. Further validation demonstrates that APYS1 has an atypical mechanism of action, not directly targeting Wag31, but perhaps an associated protein-protein interaction.