A streptomycin-resistant mutant of a virulent strain of Salm. typhimurium was less virulent to mice than the parent strain. The difference in virulence was only observed when mice were infected with small numbers of organisms. Although the mutant strain caused fewer deaths than the parent strain it remained capable of establishing persistent infection in the majority of animals.
The significant difference in the behaviour of the two strains in vivo was that after clearance from the blood multiplication in the tissues began more rapidly with the virulent strain and was progressive, whereas multiplication of the mutant was delayed, was less in degree and was apparently suppressed within a few days of infection.
The mutant strain was apparently identical antigenically with the parent strain, and was equally toxic. The mice dying of infection with this strain did so when the bacterial population had reached a level similar to that in the terminal stage of infection with the virulent strain.
The essential difference between the two strains was the speed and probability of attaining a critical final population. The mutant strain of Salm. typhimurium, both in vitro and in vivo, had a slower growth rate than the parent strain. A possible hypothesis to explain the importance of this finding in relation to the outcome of infection has been discussed.
I am indebted to the Medical Research Council for the provision of a grant towards the expenses of this investigation and to Mr T. Norris and Miss Italia S. Alderton for technical assistance.