Identification of KasA as the cellular target of an anti-tubercular scaffold

• Published in: Nature communications Vol. 7; no. 1; p. 12581
• Main Authors: Abrahams, Katherine A., Chung, Chun-wa, Ghidelli-Disse, Sonja, Rullas, Joaquín, Rebollo-López, María José, Gurcha, Sudagar S., Cox, Jonathan A. G., Mendoza, Alfonso, Jiménez-Navarro, Elena, Martínez-Martínez, María Santos, Neu, Margarete, Shillings, Anthony, Homes, Paul, Argyrou, Argyrides, Casanueva, Ruth, Loman, Nicholas J., Moynihan, Patrick J., Lelièvre, Joël, Selenski, Carolyn, Axtman, Matthew, Kremer, Laurent, Bantscheff, Marcus, Angulo-Barturen, Iñigo, Izquierdo, Mónica Cacho, Cammack, Nicholas C., Drewes, Gerard, Ballell, Lluis, Barros, David, Besra, Gurdyal S., Bates, Robert H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase - antagonists & inhibitors; 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase - genetics; 631/154/555; 631/326/22; 631/45; 631/535/1266; 64/60; 82/103; 82/58; 82/83; Animals; Antitubercular Agents - pharmacology; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - genetics; Drug dosages; Drug resistance; Drug Resistance, Bacterial - genetics; Female; Humanities and Social Sciences; Indazoles - pharmacology; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; multidisciplinary; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Optimization; Pharmaceutical sciences; Polymorphism, Single Nucleotide - genetics; Science; Science (multidisciplinary); Sulfonamides - pharmacology; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - prevention & control; United Kingdom > UK; France

Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the...