From May to July 2011, Germany was struck by the largest outbreak of hemolytic uremic syndrome (HUS) and bloody diarrhea caused by Escherichia coli
ever reported 
. A total of 3,816 cases were reported, 845 (22%) of which involved HUS. This high rate of HUS was the first indicator that the bacterial cause of illness was not a typical enterohaemorrhagic E. coli
(EHEC) strain 
. It was shown to be a highly pathogenic enteroaggregative E. coli
(EAEC) strain, which in addition carried the EHEC genes for the classical HUS-associated Shiga toxin 2 
. Notwithstanding the timeliness of the German surveillance system (reporting occurred faster than required by law) for HUS and Shiga toxin-producing E. coli
notifiable diseases 
, no less than 54 patients died. Eventually, sprouts were identified as the most likely outbreak vehicle 
. The outbreak strain was resistant to beta-lactam antibiotics and third-generation cephalosporins and was partially resistant to fluoroquinolones, but sensitive to carbapenems and ciprofloxacin 
. However, a Cochrane database review analyzing seven randomized controlled clinical trials of pediatric HUS associated with EHEC infections found no benefit of antibiotic treatment over supportive therapy alone 
. Moreover, the use of antibiotics to treat Shiga toxin producing E. coli
infections has been discouraged because it has been shown to release toxins. The genes for the Shiga toxin are actually not bacterial genes, but (bacterio)phage genes. When an E. coli
bacterium gets infected with a temperate phage harboring a Shiga toxin gene, upon integration of the phage genome (as prophage) into the bacterial genome (lysogeny), it can be expressed by the bacterium, which then becomes pathogenic. Some types of antibiotics have been shown to induce the so-called SOS response in bacteria, i.e. a ubiquitous response to DNA damage, which induces phage replication and lytic cycle 
. As such, the use of antibiotics may be helping Shiga toxin genes to spread. Phage-mediated transfer of bacterial virulence, fitness and antibiotic resistance is a negative (from the human point of view) consequence of bacterial phage coevolution.
Paradoxically, phages from a very different, constitutionally lytic genus could also help fight EHEC and EAEC. Phages do play a major role in controlling bacterial densities in the biosphere, including humans, which is the basis of sustainable phage therapy 
. For example, phages appear to be key players in ending cholera epidemics. Faruque et al
observed that seasonal epidemics of cholera inversely correlated with the prevalence of environmental cholera phages. Phages could be used therapeutically, as an additional tool or in combination with antibiotics, to treat bacterial infections that do not respond to conventional antibiotics. Importantly, they can be chosen to be harmless to the commensal bacteria, such as those of the gut microflora. The oral application of phages to humans is likely to be very safe 
and several phage based preparations were given regulatory approval and are commercially available for the decontamination of foods 
. Muniesa et al.
, in a review on experimental treatment and prevention options for HUS, reported phages to be an effective tool for disinfection of various vegetables and meat products contaminated by E. coli
strain O157. Steers that received phage by the rectal route showed a 100-fold fecal titer decrease of O157 compared to controls. In sheep, oral T4-like coliphage reduced the O157 counts in the caecum and rectum. Recently, French scientists isolated three morphologically different types of tailed phages that infect E. coli
O104:H4. The cocktail of all three phages showed sustained replication in the intestines of mice, but without decreasing the intestinal titer of O104:H4 cells 
Here we present the results of an ad hoc multidisciplinary working group, including institutions involved in infectious diseases surveillance, phage therapy and molecular biology research, which set out to isolate, select and characterize candidate therapeutic phages active against the E. coli O104:H4 outbreak strain.