title: Nutrient-starved incubation conditions enhance pyrazinamide activity against Mycobacterium tuberculosis.
abstract: Pyrazinamide (PZA) is an unconventional frontline tuberculosis drug characterized by high in vivo sterilizing activity, but poor in vitro activity. The study on the mechanism of action of PZA has attracted significant attention because of the peculiarity of PZA and its ability to shorten the tuberculosis chemotherapy. In this study, we examined the effect of nutrient-starved conditions on PZA activity in vitroat acid pH. We also examined the effect of fatty acids, benzoic acid and salicylic acid on PZA activity. The results showed that nutrient-starved conditions lowered the membrane potential of Mycobacterium tuberculosis and enhanced the activity of PZA, with 5- and 10-day starvation conditions resulting in greater enhancement than 3-day starvation. Fatty acids, benzoic acid and salicylic acid enhanced PZA activity in both normal and starved bacilli, especially in starved bacilli. These findings provide further support for the recent model of PZA action and may have implications for developing new drugs that shorten therapy.
authors.affiliation: MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Zhi-Fei
authors.initials: ZF
authors.lastname: Chen
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Fu
authors.forename: Shun-Qing
authors.initials: SQ
authors.lastname: Xu
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects*; D011718:Pyrazinamide / Q000494:pharmacology*