Bacterial cells that grow rapidly do not have time to copy their entire DNA before it is time to divide again. This means that several copying processes can take place simultaneously in one cell. Researchers at Uppsala University have clarified how the cells coordinate cell size and division time in order to maintain exactly one copy of the genome per cell. The study is presented in the scientific journal Cell.
The results explain, for example, why cell sizes can vary greatly even for genetically identical bacteria that grow under identical conditions. In the study, 10,000s of individual e-coli bacteria were examined using specially designed microscopes and self-developed image processing methods.
A cell must coordinate the copying of the genetic information so that there is always a complete copy in each daughter cell after cell division. It is especially complicated in bacteria where it takes much longer to copy the chromosome than it takes for the cell to divide. For example, for the e-coli bacterium, the copying of the DNA takes almost an hour, while the cell divides every 20 minutes. The division is thus two generations before the DNA copying, which means that several copying processes take place simultaneously in each cell.
The individual cells have a very large spread in growth rate, even under identical growth conditions. This means that even if the bacteria have the same access to nutrients, they will grow at different speeds.
— Since we now understand how DNA copying and cell division are linked in individual cells, we can also correctly predict how the spread in growth leads to a spread in cell sizes and division times, says Johan Elf.
The study is based on new microscopy methods that make it possible to measure how the copying of DNA is linked to the cell size and division cycle in each individual cell. It has also been absolutely crucial to develop new microfluidic solutions and image analysis methods that have made it possible to follow tens of thousands of individual cells for several generations.
Bacterial cells’ regulation of the cell cycle has direct counterparts in the cells of the human body. For humans, it is very important that this regulation works because dysfunctional cell cycle regulation is the reason why cancer develops.
However, the new results are not directly applicable in cancer research, but well in antibiotic research where the understanding of the bacterial growth is of central importance. The new experimental methods that have now been developed can, for example, be used to quickly measure antibiotic resistance with very high reliability and precision.
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