A Positive Selection for Nucleoside Kinases in E. coli
A) In typical cells, AZT penetrates the outer membrane, periplasm and inner membrane to be metabolized in to its triphosphate form to generate genotoxicity towards E. coli. B) When HSV-TK is exported to the periplasm AZT is phosphorylated in the periplasm; however, PhoA counteracts by dephosphorylating the AZT-MP, allowing AZT to penetrate the inner membrane causing genotoxicity. C) In cells lacking PhoA but containing periplasmic HSV-TK, AZT is phosphorylated and AZT-MP cannot cross the inner membrane. Thus, periplasmic HSV-TK provides AZT resistance to phoA–strains.