Colonization, diarrhoea and protective immunogenicity of a CFA-deficient, enterotoxin-producing Escherichia coli mutant in a non-ligated intestine experimental model.

A colonization factor antigen (CFA)-deficient mutant has been isolated that is as efficient as the CFA/I-carrying, enterotoxin-producing E. coli strain it was derived from in producing diarrhoea and colonizing the intestine in a rabbit non-ligated intestine model, the RITARD model. Infection with 10(11) mutant bacteria induced diarrhoea in 15 of the 17 rabbits challenged; corresponding diarrhoeal attack rates after challenge with similar doses of the original CFA/I-positive strain and of a non-enterotoxinogenic, non-CFA control strain were 23/24 and 0/15, respectively. Whereas the mean time of excreting the challenge strain in faeces did not differ between the mutant and the CFA/I-positive strain (4.5 and 4.3 days, respectively), it was significantly longer (p less than 0.05) than for the control strain (2.5 days). Similarly, the magnitude of the serum antibody responses to homologous O-antigen was equally high after infection with the mutant and the CFA/I-positive strain and considerably higher than after challenge with the negative control strain. An initial infection in the RITARD model with the CFA-deficient mutant offered highly significant protection against diarrhoea (p less than 0.001) as well as colonization (p less than 0.01) on subsequent challenge with the original CFA/I-positive strain. No significant protection, either against colonization or disease, was induced by initial infection with a similar dose of the control strain.