Reliable detection of pyrazinamide antitubercular activity in vitro

Pyrazinamide (PZA) is a pivotal antibiotic for the chemotherapy of tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuberculosis (Mtb). PZA is notorious for its poor in vitro activity which complicates phenotypic PZA-susceptibility testing (PPST) and likely causes inappropriate treatment of TB patients. Here, we show that PZA activity can be reliably detected using an acidic and lipid-rich culture medium mimicking conditions Mtb encounters during an infection. Our growth model could facilitate PPST to improve the treatment of TB patients and ameliorate the global surveillance of PZA resistance.