Abstract

Mycobacterium tuberculosis (Mtb) persister formation under antibiotic pressure is the main reason for long tuberculosis treatment and relapse. A key first-line antibiotic in TB treatment is pyrazinamide (PZA). Herein, we established an in vitro assay, the time to detection (TTD) assay, to identify persister formation after PZA exposure, by using the BD BACTEC™ MGIT™ 960 system. After treatment of Mtb H37Rv with PZA even at 20 times the MIC, not all bacteria were killed, and persisters formed in the culture. Our findings may explain the reasons for relapse after treatment. Moreover, the TTD assay developed herein may provide a valuable tool for research on persister formation under the pressure of various antibiotics.

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