Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Mycobacterium bovis exhibits natural resistance to pyrazinamide (PZA), a key antituberculosis drug.
• PZA monoresistance in Mycobacterium tuberculosis complex isolates has historically been considered indicative of M. bovis.

Purpose of the Study:

• To investigate whether all PZA monoresistant isolates are indeed M. bovis.
• To characterize the genetic basis of PZA monoresistance in Mycobacterium tuberculosis complex isolates.

Main Methods:

• Phenotypic susceptibility testing using BACTEC radiometric method.
• Genotypic analysis including pncA gene sequencing and oxyR PCR-restriction fragment length polymorphism (RFLP).
• Retesting of PZA monoresistant isolates reported by local laboratories in California.

Main Results:

• Out of 11 retested isolates, 6 were susceptible M. tuberculosis, 1 was PZA-monoresistant M. bovis, and 1 was M. bovis BCG.
• Three isolates were identified as PZA-monoresistant M. tuberculosis, each with unique pncA gene mutations.
• Genetic analysis confirmed species identification and identified novel pncA mutations in PZA-monoresistant M. tuberculosis.

Conclusions:

• PZA monoresistance is not an absolute marker for M. bovis and can occur in M. tuberculosis.
• Specific mutations in the pncA gene are associated with PZA monoresistance in M. tuberculosis.
• This study reports the first cases of PZA-monoresistant M. tuberculosis in the United States.