The intricacy of bacterial epigenetics: DNA methylation-dependent phase variation and the cell cycle in E. coli

All living cells must coordinate a vast number of molecular processes to allow metabolism, cell division and growth to occur at appropriate times. The complex regulatory networks that are responsible for this are slowly being elucidated. Due to the complex nature of cells of higher organisms, studies on bacteria can be very informative. Furthermore, bacteria can be harmful, for example pathogens that cause illness, or helpful, as in wastewater treatment. Thus, efforts that contribute to our understanding of how these single cell organisms respond to and adapt to their varied environments can help us harness their powers to our benefit.

Understanding what determines the composition of an entire bacterial population affects the interactions between the bacteria and their environment, like the body, and thus indirectly informs the studies on how we fight disease.

In this project, the regulation of a bacterial surface protein was examined. Specifically, in the bacterium Escherichia coli the regulation of the adhesion and aggregation protein called Ag43 was studied. This protein is found on many Escherichia coli strains and is believed to help it stick to surfaces. In that case, if it is a pathogenic E. coli it may help lead to disease and chronic infection.
The process that leads to Ag43 production by a bacterium is unusual since it relies in part on modification of the genetic material. Whether or not the genetic material is modified can vary, and this provides the means by which the information to express Ag43 or not is passed on from mother to daughter cell, which is a process called epigenetic regulation. This study examined how the modification state of the genetic material, DNA, is inherited, yet is liable to change in about one in a 1000 cells per generation. It was shown that obtaining daughter cells without the modification tag (a methyl group) from a mother cell with the tag is a process that is sensitive to variations in concentrations of specific proteins in the cell. In contrast, inheriting the genetic material without the tag was found to be insensitive to these variations. The effect is that bacteria that are programmed to make this protein are re-programmed to switch production off as a result of even minor changes.

Understanding what determines the composition of an entire bacterial population affects the interactions between the bacteria and their environment, like the body, and thus indirectly informs the studies on how we fight disease. Understanding how this switch that controls Ag43 expression works may in the future help identify new strategies to interfere with the production of this and similarly regulated factors that facilitate virulence of E. coli and the closely related pathogen Salmonella. Factors and processes that can be effectively and safely targeted for drug development can be identified. The new insights into the stability of the inheritance of the methyl group may also inform studies in higher organisms where a similar process is known to be a feature related to the normal development but also in diseases like cancer.