title: Missense Mutations in the Unfoldase ClpC1 of the Caseinolytic Protease Complex Are Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis.
abstract: Previously, we showed that mutations in Mycobacterium tuberculosis panD, involved in coenzyme A biosynthesis, cause resistance against pyrazinoic acid, the bioactive component of the prodrug pyrazinamide. To identify additional resistance mechanisms, we isolated mutants resistant against pyrazinoic acid and subjected panD wild-type strains to whole-genome sequencing. Eight of the nine resistant strains harbored missense mutations in the unfoldase ClpC1 associated with the caseinolytic protease complex.
authors.affiliation: Antibacterial Drug Discovery Laboratory, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Michelle
authors.initials: M
authors.lastname: Yee
authors.affiliation: Antibacterial Drug Discovery Laboratory, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Pooja
authors.initials: P
authors.lastname: Gopal
authors.affiliation: Antibacterial Drug Discovery Laboratory, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore micdickt@nus.edu.sg.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dick
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; C005296:pyrazinoic acid
keywords: ClpC1; Mycobacterium tuberculosis; caseinolytic protease; pyrazinamide; resistance