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.

journal_name

Chemotherapy

journal_title

Chemotherapy

authors

Huang Q,Chen ZF,Li YY,Zhang Y,Ren Y,Fu Z,Xu SQ

doi

10.1159/000107723

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

338-43

issue

5

eissn

0009-3157

issn

1421-9794

pii

000107723

journal_volume

53

pub_type

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