ANTI-BACTERIAL ACTIVITY OF 2',3'-DIDEOXYADENOSINE INVIVO AND INVITRO

2'',3''-Dideoxyadenosine (DDA) not only possesses antibacterial activity in vitro against a variety of Enterobacteriaceae but also is 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 inactive in vivo, indicating that a high degree of structural specificity was required for activity. The synthesis of DNA was inhibited by DDA in those strains susceptible in vitro to DDA; RNA and protein syntheses were not affected. The concentration of DDA which inhibited bacterial DNA synthesis by 50% was calculated based on the relative rates of DNA 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.