Phage-Bacteria Interactions

Bacteriophages, viruses that can infect bacteria, have been researched for over 100 years. Thanks to the study of phages and their interactions with their host cells, some important basic biological principles of genetics have been deciphered. Due to the increasing problems caused by multidrug-resistant bacteria and the possibility of combating harmful bacteria with the help of phages, research into phages, their interactions with bacteria and resistance mechanisms is experiencing a renaissance. The major influence of phages on bacterial evolution, diversity and the “arms race” between bacteria and phages is becoming increasingly apparent (Salmond & Fineran, 2015).

One of the most common and mobile defense mechanisms bacteria utilize against phages are restriction-modification systems (R-M systems). Classical R-M systems consist of a DNA-modifying methyltransferase (MT) and a DNA-cutting restriction endonuclease (RE), whereby MT and RE of a R-M system recognize the same DNA sequences. The methylation of the DNA by the MT protects the DNA from the enzymatic activity of the associated RE (Loenen et al., 2013).

This simple arrangement allows bacteria to distinguish between their own and foreign DNA and thus to defend themselves against, for example, phage DNA after an infection.

Since the effect of RE without the corresponding DNA modifications by MT would be toxic to the bacteria and the effect of MT on phage DNA would lead to phage particles that are resistant to the R-M system, strict regulation of MT and RE activities is essential. MT and RE activities are regulated in some R-M systems via protein-protein interactions, while in others gene expression of MT- and RE-encoding genes is transcriptionally regulated (Loenen et al., 2013).

In some R-M systems, gene expression of MT- and RE-encoding genes is regulated by DNA modification of the corresponding MT. This is also the case in the CfrBI R-M system. The DNA methylation alters the gene expression (Beletskaya et al., 2000).

In our research, we address the question of which factors influence the gene expression dynamics of such an R-M system and what consequences this has for the cell and ultimately the defense against phages. Furthermore, it is an interesting example to study the influence of epigenetic DNA modifications on gene expression and evolution of bacteria.

Beletskaya, I.V., Zakharova, M.V., Shlyapnikov, M.G., Semenova, L.M. & Solonin, A.S. (2000) DNA methylation at the CfrBI site is involved in expression control in the CfrBI restriction-modification system. Nucleic Acids Res. 28 (19): 3817–3822.

Loenen, W.A.M., Dryden, D.T.F., Raleigh, E.A., Wilson, G.G. & Murray, N.E. (2013) Highlights of the DNA cutters: a short history of the restriction enzymes. Nucleic Acids Res. 42 (1): 3-19.

Salmond, G.P.C. & Fineran, P.C. (2024) A century of the phage: past, present and future. Nat Rev Microbiol. 13 (12): 777-786.