Abstract
We recently reported a genome-wide screen for extended stationary phase survival in Escherichia coli. One of the mutants recovered is deleted for ubiG, which encodes a methyltransferase required for the biosynthesis of ubiquinone. The ubiG mutant exhibits longer lifespan, as well as enhanced resistance to thermal and oxidative stress compared to wt at extracellular pH9. The longevity of the mutant, as well as its resistance to the superoxide-generating agent paraquat, is partially dependent on the hypoxia-inducible transcription factor ArcA. A microarray analysis revealed several genes whose expression is either suppressed or enhanced by ArcA in the ubiG mutant. TdcA is a transcription factor involved in the transport and metabolism of amino acids during anaerobic growth. Its enhanced expression in the ubiG mutant is dependent on ArcA. Our data are consistent with the hypothesis that ArcA and TdcA function in the same genetic pathway to increase lifespan and enhance oxidative stress resistance in the ubiG mutant. Our results might be relevant for the elucidation of the mechanism of lifespan extension in mutant mice and worms bearing mutations in ubiquinone biosynthetic genes.
Highlights
At the population level, Escherichia coli maintained in batch culture in the complex, rich medium LuriaBertani broth (LB) goes through several phases [1]
ArcA is a transcription factor that contributes to the adaptation of E. coli to hypoxic conditions by suppressing genes required for oxidative metabolism and activating genes involved in nonoxygen-dependent metabolic functions [6]
Since the ubiG mutant appears to adopt a hypoxia-like metabolism and because we previously showed that acetate production and uptake are required for the extended lifespan of the lipA strain [5], we measured the concentration of extracellular acetate in the ubiG strain and found it to be higher than that of wt
Summary
Escherichia coli maintained in batch culture in the complex, rich medium LuriaBertani broth (LB) goes through several phases [1]. The initial phase of exponential proliferation is followed by a period of stasis during which no further increase in biomass is observed; this period, which is known as stationary phase, is followed by the death phase at the end of which 1-10% of the initial population retains viability as measured either by plate counts or by staining with fluorescent dyes [2]. The progressive loss of viability observed during death phase is reminiscent of the exponential increase in mortality rates over time that characterizes aging in higher organisms [3]. ArcA is a transcription factor that contributes to the adaptation of E. coli to hypoxic conditions by suppressing genes required for oxidative metabolism and activating genes involved in nonoxygen-dependent metabolic functions [6]
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