OBJECTIVE: To characterize the correlation of the mutations in the pncA gene encoding pyrazinamidase (PZase) of Mycobacterium tuberculosis to a loss of PZase activity and development of pyrazinamide (PZA) resistance. DESIGN: The association of PZase activity, minimum inhibitory concentrations (MICs), and mutations in the pncA gene of M. tuberculosis isolated in mostly Asian countries was investigated. RESULTS: One hundred thirty-five out of 168 isolates were PZase positive, and 33 were negative. The MICs of PZA at pH 6.0 were over 400 micrograms/ml for all 33 PZase-negative isolates, while those of PZase-positive isolates were equal to or less than 200 micrograms/ml. Among 33 PZase-negative isolates sequenced, 32 (97%) had mutations within the pncA gene. A mutation was seen in various regions throughout the pncA gene. It was surprising that all three strains of in vitro selected PZA resistant mutants were PZase-positive and showed no change in the pncA gene. These results indicate that additional mechanisms may be involved in PZA resistance. No mutations were observed in all of 135 PZase-positive M. tuberculosis isolates tested, indicating that mutations in the pncA gene could be involved in the loss of PZase activity. CONCLUSIONS: Sequencing analysis of the pncA gene should provide rapid diagnosis of PZA resistant clinical isolates of M. tuberculosis.
OBJECTIVE: To characterize the correlation of the mutations in the pncA gene encoding pyrazinamidase (PZase) of Mycobacterium tuberculosis to a loss of PZase activity and development of pyrazinamide (PZA) resistance. DESIGN: The association of PZase activity, minimum inhibitory concentrations (MICs), and mutations in the pncA gene of M. tuberculosis isolated in mostly Asian countries was investigated. RESULTS: One hundred thirty-five out of 168 isolates were PZase positive, and 33 were negative. The MICs of PZA at pH 6.0 were over 400 micrograms/ml for all 33 PZase-negative isolates, while those of PZase-positive isolates were equal to or less than 200 micrograms/ml. Among 33 PZase-negative isolates sequenced, 32 (97%) had mutations within the pncA gene. A mutation was seen in various regions throughout the pncA gene. It was surprising that all three strains of in vitro selected PZA resistant mutants were PZase-positive and showed no change in the pncA gene. These results indicate that additional mechanisms may be involved in PZA resistance. No mutations were observed in all of 135 PZase-positive M. tuberculosis isolates tested, indicating that mutations in the pncA gene could be involved in the loss of PZase activity. CONCLUSIONS: Sequencing analysis of the pncA gene should provide rapid diagnosis of PZA resistant clinical isolates of M. tuberculosis.
Authors: H J Marttila; M Marjamäki; E Vyshnevskaya; B I Vyshnevskiy; T F Otten; A V Vasilyef; M K Viljanen Journal: Antimicrob Agents Chemother Date: 1999-07 Impact factor: 5.191
Authors: M Mestdagh; P A Fonteyne; L Realini; R Rossau; G Jannes; W Mijs; K A De Smet; F Portaels; E Van den Eeckhout Journal: Antimicrob Agents Chemother Date: 1999-09 Impact factor: 5.191
Authors: Ailyn C Pérez-Osorio; David S Boyle; Zachary K Ingham; Alla Ostash; Romesh K Gautom; Craig Colombel; Yolanda Houze; Brandon T Leader Journal: J Clin Microbiol Date: 2011-12-07 Impact factor: 5.948
Authors: Niuris C Mirabal; Sergio L Yzquierdo; Dihadenys Lemus; Mariela Madruga; Yoslaine Milián; Miguel Echemendía; Howard Takiff; Anandi Martin; Patrick Van der Stuyf; Juan Carlos Palomino; Ernesto Montoro Journal: J Clin Microbiol Date: 2010-06-16 Impact factor: 5.948
Authors: Dao Nguyen; Paul Brassard; Jennifer Westley; Louise Thibert; Melanie Proulx; Kevin Henry; Kevin Schwartzman; Dick Menzies; Marcel A Behr Journal: J Clin Microbiol Date: 2003-07 Impact factor: 5.948