PMID:3551832

Citation	Elwell, LP, Ferone, R, Freeman, GA, Fyfe, JA, Hill, JA, Ray, PH, Richards, CA, Singer, SC, Knick, VB and Rideout, JL (1987) Antibacterial activity and mechanism of action of 3'-azido-3'-deoxythymidine (BW A509U).Antimicrob. Agents Chemother. 31:274-80
Abstract	The thymidine analog 3'-azido-3'-deoxythymidine (BW A509U; azidothymidine [AZT]) had potent bactericidal activity against many members of the family Enterobacteriaceae, including strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, Shigella flexneri, and Enterobacter aerogenes. AZT also had bactericidal activity against Vibrio cholerae and the fish pathogen Vibrio anguillarum. AZT had no activity against Pseudomonas aeruginosa, gram-positive bacteria, anaerobic bacteria, Mycobacterium tuberculosis, nontuberculosis mycobacteria, or most fungal pathogens. Several lines of evidence indicated that AZT must be activated to the nucleotide level to inhibit cellular metabolism: AZT was a substrate for E. coli thymidine kinase; spontaneously arising AZT-resistant mutants of E. coli ML-30 and S. typhimurium were deficient in thymidine kinase; and intact E. coli ML-30 cells converted [3H]AZT to its mono-, di-, and triphosphate metabolites. Of the phosphorylated metabolites, AZT-5'-triphosphate was the most potent inhibitor of replicative DNA synthesis in toluene-permeabilized E. coli pol A mutant cells. AZT-treated E. coli cultures grown in minimal medium contained highly elongated cells consistent with the inhibition of DNA synthesis. AZT-triphosphate was a specific DNA chain terminator in the in vitro DNA polymerization reaction catalyzed by the Klenow fragment of E. coli DNA polymerase I. Thus, DNA chain termination may explain the lethal properties of this compound against susceptible microorganisms.
Links	PubMed
Keywords	Antiviral Agents; DNA Replication; DNA, Bacterial; Drug Resistance, Microbial; Enterobacteriaceae; Escherichia coli; HIV; Kinetics; Microbial Sensitivity Tests; Mutation; Thymidine; Thymidine Kinase; Vibrio; Zidovudine
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Phenotype of	Taxon Information	Genotype Information (if known)	Condition Information	OMP ID	OMP Term Name	ECO ID	ECO Term Name	Notes	Status
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: ML-30 NCBI Taxon ID: 83333	Genotype of Reference Strain: tdk+ Genotype of Experimental Strain : tdk mutation in ML-30	Reference Condition:
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