The Applicability of the Hypothesis of Independent Action to Fatal Infections in Mice given Salmonella typhimurium by Mouth

SUMMARY: Mice were challenged by mouth with a suspension containing equal numbers of streptomycin-sensitive (Str−) and streptomycin-resistant (Str+) variants of Salmonella typhimurium. These variants were of equal virulence but the Str+ variant grew more slowly in vivo than the Str− variant. The LD50 dose contained c. 5 × 105bacteria. Heart blood obtained from mice dying from many LD50 doses nearly always contained a great excess of the Str− variant, but blood from mice dying from less than one LD50 dose contained either Str−, Str+, or a mixture of Str− and Str+ variants. The appearance of the Str+ variant alone in the latter mice strongly suggests that these fatal infections were initiated by a very small number of organisms or possibly by a single organism. It is therefore concluded that these organisms were acting independently. In this system, it is likely that any bacterium which enters the tissues from the gut can initiate a fatal infection and that the probability of effecting such an entrance almost entirely determines the probability of an inoculated bacterium causing a fatal infection.