Enteropathogenic Escherichia coli strains are foodborne pathogens, which are often highly resistant to phages that efficiently lyse E. coli K12 strains. However, the phage defense mechanisms that convey the strong protection in pathogenic E. coli as the natural hosts presently remain poorly understood.

In our project, we aim at elucidating (1) the phage spectrum, (2) the synergy and (3) the molecular mechanisms of novel nuclease-based phage defense systems in enteropathogenic E. coli. Based on our biochemical and structural data, the defense systems might discriminate phage and host DNA by methylation and degrade non-methylated phage DNA at specific restriction sites. Overall, our project will contribute to a better understanding of phage defense mechanisms in enteric pathogens and to the development of potential inhibitors of phage defense systems for support of phage-based therapies.