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Methods to Inhibit Bacterial Pyomelanin Production and Determine the Corresponding Increase in Sensitivity to Oxidative Stress
Published on: August 31, 2015
SELECTIVE REVERSIBLE INHIBITION OF MICROBIAL GROWTH WITH PYRITHIAMINE
1Laboratories of The Rockefeller Institute for Medical Research.
The Journal of Experimental Medicine
|October 30, 2009
Summary
Pyrithiamine, a thiamine analog, inhibited microbial growth, particularly in species reliant on intact thiamine. Resistance in other species was not explained by thiamine synthesis.
Area of Science:
- Microbiology
- Biochemistry
Background:
- Thiamine (vitamin B1) is essential for microbial growth.
- Pyrithiamine, a synthetic pyridine analog of thiamine, is investigated for its biological activity.
Purpose of the Study:
- To investigate the inhibitory effects of pyrithiamine on microbial growth.
- To correlate pyrithiamine's inhibitory action with thiamine requirements of various microorganisms.
- To explore mechanisms of resistance to pyrithiamine.
Main Methods:
- Testing the growth inhibition of diverse microbial species (bacteria, yeasts, molds) using pyrithiamine.
- Assessing the influence of thiamine and its components (pyrimidine, thiazole) on growth and inhibition.
- Investigating thiamine synthesis in pyrithiamine-resistant species.
Main Results:
- Pyrithiamine inhibited growth in microbial species that utilized thiamine or its components for growth.
- Inhibition was most pronounced in organisms requiring intact thiamine, with half maximal inhibition at 0.03 gamma/cc.
- Sufficient thiamine supplementation consistently reversed pyrithiamine-induced growth inhibition.
- Resistance in certain species was not attributable to endogenous thiamine synthesis.
Conclusions:
- Pyrithiamine's inhibitory effect is specific to microorganisms dependent on thiamine or its precursors.
- The degree of inhibition correlates with the specificity of thiamine utilization.
- Microbial resistance to pyrithiamine is complex and not solely explained by self-synthesis of thiamine.
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