Effectiveness of Phages in Treating Experimental Escherichia coli Diarrhoea in Calves, Piglets and Lambs

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Abstract
A mixture of 2 phages, B44/1 and B44/2, protected calves against a potentially lethal oral infection with an O9:K30,99 enteropathogenic strain of E. coli, called B44, when given before, but not after, the onset of diarrhea; a mixture in which phage B44/2 was replaced by phage B44/3 was effective after the onset of diarrhea. Calves that responded to phage treatment had much lower numbers of E. coli B44 in their alimentary tract than untreated calves. Usually, high numbers of phage B44/1 and rather lower numbers of phage B44/2 or B44/3 were present in the alimentary tract of these animals. At death, most calves that had not responded to treatment with phages B44/1 and B44/2 had high numbers of mutant E. coli B44 resistant to phage B44/1 in their small intestine. Phage-treated calves that survived E. coli infection continued to excrete phage in their feces, at least until the numbers of E. coli B44 also excreted were low. The phages survived longer than E. coli B44 in fecal samples taken from phage-treated calves and exposed to the atmosphere in an unheated animal house. Calves inoculated orally with fecal samples from phage-treated calves that contained sufficient E. coli B44 to cause a lethal infection remained healthy. A mixture of 2 phages, P433/1 and P433/2, and phage P433/1 alone cured diarrhea in piglets caused by an O20:K101,987P strain of E. coli called P433. The numbers of the infecting bacteria and phages in the alimentary tract of the piglets resembled those in the calves. Another phage given to lambs 8 h after they were infected with an O8:K85,99 enteropathogenic strain of E. coli, called S13, reduced the numbers of these organisms in the alimentary tract and had an ameliorating effect on the course of the disease. No phage-resistant mutants of E. coli S13 were isolated from the lambs. The only mutants of E. coli B44 and P433 that emerged in the calves and piglets were K30- or K101- and resistant to phage B44/1 or P433/1, respectively; those tested were much less virulent than their parent strains.