Antibacterial activity of 2',3'-dideoxyadenosine in vivo and in vitro

2',3'-Dideoxyadenosine (DDA) was shown not only to possess antibacterial activity in vitro against a variety of Enterobacteriaceae, but also to be effective in vivo, DDA was active in experimental mouse infections by the oral route against 5 Salmonella strains, 2 of 3 Arizona strains, 5 of 7 Citrobacter strains, 3 of 8 Klebsiella strains, 3 of 5 Escherichia strains, 1 of 3 Shigella strains, and 3 of 15 Serratia strains at concentrations generally well below the toxic level. Closely related compounds, with the exception of 2',3'-dideoxyinosine, were found to be inactive in vivo, indicating that a high degree of structural specificity was required for activity. The synthesis of deoxyribonucleic acid was inhibited by DDA in those strains susceptible in vitro to DDA, whereas ribonucleic acid and protein syntheses were not affected. The concentration of DDA which inhibited bacterial deoxyribonucleic acid synthesis by 50% was calculated based on the relative rates of deoxyribonucleic acid synthesis in ;the absence and in the presence of DDA. This value correlated well with the minimal inhibitory concentration determined by the in vitro broth dilution assay but not always with in vivo activity determined by the mouse protection test.