Relationship between Pyrazinamide Resistance, Loss of Pyrazinamidase Activity, and Mutations in the pncALocus in Multidrug-Resistant Clinical Isolates of Mycobacterium tuberculosis

ABSTRACTSixty-two Mycobacterium tuberculosisisolates were tested for pyrazinamidase activity, and their pyrazinamide susceptibility was determined by the radiometric method. Sequencing ofpncAgenes in the 23 resistant strains revealed mutations in 16 pyrazinamidase-negative strains, 11 of which had not been previously described. Six isolates containing wild-typepncAmight possess alternative resistance mechanisms.