Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli

What is it about?

A cell’s DNA can acquire errors over the course of its lifetime. These errors, known as mutations, are often harmful and can cripple the cell. However, some mutations are needed to enable a cell or organism to adapt to changes in its environment. Since there is a trade-off between acquiring beneficial mutations versus harmful ones, cells carefully balance how often they acquire new mutations. Cells have several mechanisms that limit the number of mutations by correcting errors in DNA. Occasionally these repair mechanisms may fail so that a small number of cells in a population accumulate mutations more quickly than other cells. This process is known as “hypermutation” and it enables some cells to rapidly adapt to changing conditions in order to avoid the entire population from becoming extinct. So far, studies on hypermutation have largely been carried out under conditions that are mildly stressful to the cells, which only cause low frequency of hypermutation. However, little is known about the role of this process in cells under near-lethal levels of stress, for example, when drugs target bacteria or cancer cells in the human body. Swings et al. studied hypermutation in populations of a bacterium called Escherichia coli exposed to levels of alcohol that cause the bacteria to experience extreme stress. The experiments show that hypermutation occurs rapidly in these conditions and is essential for bacteria to adapt to the level of alcohol and avoid extinction. Populations of bacteria in which hypermutation did not occur were unable to develop tolerance to the alcohol and perished. Further experiments show that an individual population of bacteria can alter the rate of mutation (that is, how often new mutations arise) several times as a result of changing stress levels. The findings of Swings et al. suggest that hypermutation can rapidly arise in populations of cells that are experiencing extreme stress. Therefore, this process may pose a serious risk in the development of drug resistant bacteria and cancer cells. In the future, developing new drugs that target hypermutation may help to fight bacterial infections and cancer.

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