The interaction between Escherichia coli O157:H7 and its specific bacteriophage PP01 was investigated in chemostat continuous culture. Following the addition of bacteriophage PP01, E. coli O157:H7 cell lysis was observed by over 4 orders of magnitude at a dilution rate of 0.876 h ؊1 and by 3 orders of magnitude at a lower dilution rate (0.327 h ؊1 ). However, the appearance of a series of phage-resistant E. coli isolates, which showed a low efficiency of plating against bacteriophage PP01, led to an increase in the cell concentration in the culture. The colony shape, outer membrane protein expression, and lipopolysaccharide production of each escape mutant were compared. Cessation of major outer membrane protein OmpC production and alteration of lipopolysaccharide composition enabled E. coli O157:H7 to escape PP01 infection. One of the escape mutants of E. coli O157:H7 which formed a mucoid colony (Mu) on Luria-Bertani agar appeared 56 h postincubation at a dilution rate of 0.867 h ؊1 and persisted until the end of the experiment (ϳ200 h). Mu mutant cells could coexist with bacteriophage PP01 in batch culture. Concentrations of the Mu cells and bacteriophage PP01 increased together. The appearance of mutant phage, which showed a different host range among the O157:H7 escape mutants than wild-type PP01, was also detected in the chemostat culture. Thus, coevolution of phage and E. coli O157:H7 proceeded as a mutual arms race in chemostat continuous culture.It has been suggested that most Escherichia coli O157:H7 infections in humans are food-borne illnesses and that dairy and beef cattle are reservoirs of E. coli O157:H7 (10). In addition, E. coli O157:H7 seems to persist in food processing because of its acid and heat tolerance (18). Contamination with E. coli O157:H7 may frequently occur at various stages of food processing and drive up the potential for human infection (7). Thus, the elimination of E. coli O157:H7 from the animal intestine might be effective for the prevention of the infection. In previous reports, dietary manipulations, such as a fasting followed by a reseeding or administration of Lactobacillus casei, induced the clearance of E. coli O157:H7 from animal gastrointestinal tracts (13,17,22).Previous reports also discussed the role of bacteriophage in reducing enteropathogenic bacteria in live animals and gastrointestinal models (2,4,12,19,23,25). It is known that the elevated levels of virulent phage in human feces correlate with diseased conditions (8). Thus, phage may play an important role in affecting pathogenic bacteria in intestinal environments.The emergence of infectious disease caused by drug-resistant bacteria requires alternatives to conventional antibiotics (1, 3, 6, 26). Phage therapy is one possible option, and it can provide an economical tool for controlling pathogens in the intestinal tract without affecting the viability of other normal flora (14, 15). Three virulent E. coli O157 antigen-specific phages, designated KH1, KH4, and KH5, have been analyzed in an attempt to control ...