SUMMARY: Albicidin blocked DNA synthesis in intact cells of a PolA EndA strain, and in permeabilized cells supplied with all necessary precursor nucleotides, indicating a direct effect on prokaryote DNA replication. Replication of phages T4 and T7 was also blocked by albicidin in albicidin-sensitive (Alb) but not in albicidin-resistant (Alb) host-cells. All stable spontaneous Alb mutants of simultaneously became resistant to phage T6. The locus determining albicidin sensitivity mapped at , the structural gene for an outer-membrane protein used as a receptor by phage T6 and involved in transport through the outer membrane of nucleosides present at submicromolar extracellular concentrations. Albicidin does not closely resemble a nucleoside in structure. However, Alb strains rapidly accumulated both nucleosides and albicidin from the surrounding medium whereas the Alb mutants were defective in uptake of nucleosides and albicidin at low extracellular concentrations. An insertion mutation blocking Tsx protein production also blocked albicidin uptake and conveyed albicidin resistance. Albicidin supplied at approximately 0.1 μM blocked DNA replication within seconds in intact Alb cells, but a 100-fold higher albicidin concentration was necessary for a rapid inhibition of DNA replication in permeabilized cells. We conclude that albicidin is effective at very low concentrations against because it is rapidly concentrated within cells by illicit transport through the -encoded outer-membrane channel normally involved in nucleoside uptake. Albicidin resistance results from loss of the mechanism of albicidin transport through the outer membrane.


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