Phages against porcine post-weaning diarrhea due to O149 Escherichia coli
The objective of this study was to isolate, characterize, and evaluate phages that might be used in prevention and treatment of porcine post-weaning diarrhea due to O149 enterotoxigenic 'E. coli' (ETEC). Serotype O149:H10 was especially targeted because this is the dominant ETEC serotype and strains are highly virulent. Six phages (N1-N6) that lysed O149:H10 ETEC and three (O7-O9) that lysed O149:H43 ETEC were isolated from pig sewage from Ontario pig farms. Phages Nl-N6 lysed 99-100% of 85 O149:H10 ETEC, 0-12% of 42 O149:H43 ETEC, 3-35% of 37 non-O149 porcine ETEC, and 6-68% of the 72 strains of the ECOR collection. Phages O7-O9 lysed 86-98% of the O149:H43 ETEC, 2-53% of the O149:H10 ETEC, and 24-41% of the non-O149 porcine ETEC. The phages were susceptible to extremes of pH. All nine phages had necks and contractile tails typical of the 'Myoviridae.' The estimated genome sizes of phages Nl-N6 were 42-50 kb. Phage N1 was shown to consist of a circularly permuted genome of 52,976 bp, with terminal repeats and a G+C content of 44%. There were 75 putative genes, all reading from left to right on the same DNA strand. There was no integrase gene and no 'attp' region. The phage was unique as the genes involved in morphogenesis were related to genes of the ' Myoviridae' whereas the remaining genes were related to genes of the T7 group of phages belonging to the 'Podoviridae.' Phages N1-N6 individually and a combination of phages N1, N2, and O7 were investigated for their effectiveness as a prophylactic measure in weaned pigs that were concurrently challenged with an O149:H10 ETEC. Also, a mixture of phages N1 and N6 was evaluated as therapy after diarrhea developed following a similar experimental challenge. In both modes, individually and in combination, administration of the phages typically resulted in improvement in weight gain, and reduction in the duration and severity of diarrhea, and decreased excretion of the challenge ETEC as compared with the control pigs. These studies indicate that the N phages are good candidates for development for prophylactic and therapeutic strategies for O149:H10 ETEC diarrhea in weaned pigs.