A coordinated SOS-response is inducing the auto-lysis of E. coli K-12 MG1655 by ΦO104

Infections with enterohemorrhagic Escherichia coli (EHEC) can result in life-threatening haemolytic uremic syndrome (HUS) and ultimately in death. The German outbreak strain from 2011 E. coli O104:H4 was unusual, because the infections affected mainly adults and progressed in ~25% of the cases to HUS. The exceptional virulence of the strain was attributed to its "hybrid" virulence gene content, as it encoded aggregative adherence fimbria characteristic for enteroaggregative E. coli, as well as a Shiga toxin (STX) 2 encoding phage, the hallmark of EHEC. However, little is known about the role of the specific patient microbiome on the course of the disease. Mixed cultures of EHEC and STX phage-susceptible E. coli were shown to produce higher amounts of STX than pure EHEC cultures, indicating a potential role of the microbiota to overall toxin production. Moreover, it was shown that certain STX phages, including ΦO104, have replication origins different from lambdoid EHEC phages and a less stable lysogenic state. We show here that ΦO104 and the EHEC O157:H7-derived phages PA2 and PA8 are unstable in E. coli MG1655. We show that the stability of the phages is sensitive to environmental factors, e.g. growth temperature, growth medium composition and carbon source, and partially to genetic factors, e.g. luxS and lsr. This indicated that the auto-activation of the phages in E. coli MG1655 is a regulated process, however different from the respective wild types, in which the lysogenic state is much more stable. By using recA mutants, we show that the SOS response is the essential signal for phage activation in E. coli MG1655. By using an SOS reporter, we show that coordinated SOS response in the absence of an external inducer – that is completely absent in E. coli O104:H4 - precedes the lysis of E. coli MG1655. Moreover, we show that all environmental factors that are stabilizing the phage are as well reducing the extent of the SOS response in the lysogens. We discuss the potential mechanism underlying the phage activation, the role of the specific type of phage in the outcome of the disease, and potential therapeutic options for this aspect of the disease.