2014
DOI: 10.1111/mmi.12489
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Methylglyoxal resistance in Bacillus subtilis: contributions of bacillithiol‐dependent and independent pathways

Abstract: SummaryMethylglyoxal (MG) is a toxic by-product of glycolysis that damages DNA and proteins ultimately leading to cell death. Protection from MG is often conferred by a glutathione-dependent glyoxalase pathway. However, glutathione is absent from the low-GC Gram-positive Firmicutes, such as Bacillus subtilis. The identification of bacillithiol (BSH) as the major low-molecularweight thiol in the Firmicutes raises the possibility that BSH is involved in MG detoxification. Here, we demonstrate that MG can rapidly… Show more

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Cited by 69 publications
(69 citation statements)
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“…Mutants lacking KefB/ KefC systems are highly sensitive to MG compared with the parent strain (Ferguson et al, 1993). Consistent with previous work in E. coli , a similar system was found to occur with the KhtSTU potassium efflux pump in B. subtilis , albeit activation was attributed to S-lactoylbacillithiol instead of S-lactoylglutathione (Chandrangsu et al, 2014). Although we found the strains included in this study do not produce S-lactoylglutathione as a metabolic intermediate, the inherently low intracellular pH of Lactobacillus likely offers protection from MG toxicity.…”
Section: Discussionsupporting
confidence: 87%
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“…Mutants lacking KefB/ KefC systems are highly sensitive to MG compared with the parent strain (Ferguson et al, 1993). Consistent with previous work in E. coli , a similar system was found to occur with the KhtSTU potassium efflux pump in B. subtilis , albeit activation was attributed to S-lactoylbacillithiol instead of S-lactoylglutathione (Chandrangsu et al, 2014). Although we found the strains included in this study do not produce S-lactoylglutathione as a metabolic intermediate, the inherently low intracellular pH of Lactobacillus likely offers protection from MG toxicity.…”
Section: Discussionsupporting
confidence: 87%
“…Thiol-independent MG detoxification is catalyzed by broad-specificity aldo-keto reductases, several of which have been characterized in E. coli (Ko et al, 2005). Previously determined in B. subtilis , the aldo-keto reductase, YhdN, that converts MG to acetol was reported as the single most important detoxification route for this organism, by comparing MG sensitivity between yhdN null, glyoxalase null, and bacillithiol null strains (Chandrangsu et al, 2014). …”
Section: Discussionmentioning
confidence: 99%
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“…Methylglyoxal, a highly reactive dicarbonyl compound, is a toxic by-product of glycolysis. It is synthesized by methylglyoxal synthase under conditions of excessive carbon flux or phosphate limitation, which lead to an imbalance in the metab- olism between the carbon rate acquisition and the glycolysis (35). The toxicity of methylglyoxal is due to its ability to interact with the nucleophilic centers of macromolecules.…”
Section: Resultsmentioning
confidence: 99%
“…Therefore, the formation of methylglyoxal has to be tightly controlled, and the bacterium needs efficient mechanisms for its disposal. Indeed, three pathways for the degradation of methylglyoxal to lactate or acetol have been discovered in B. subtilis (28).…”
Section: Introductionmentioning
confidence: 99%