Mechanism of resistance to 2,6-diaminopurine in Salmonella typhimurium

2,6-Diaminopurine-resistant mutants derived from Salmonella typhimurium strain LT-2 showed a decreased capacity to incorporate 2,6-diaminopurine. However, they differed in their ability to take up adenine from the medium. The mutant, dap- r-6, which showed increased sensiivity to adenine inhibition, incorporated adenine at the same rate as LT-2. On the other hand, dap- r-3, which was resistant to adenine inhibition, showed a reduced incorporation of this purine. Incorporation of hypoxanthine, guanine, and xanthine were unaffected in this mutant. The 5-amino-4-imidazole carboxamide, an intermediate in purine biosynthesis, was incorporated poorly by both LT-2 and dap- r-3. Examination of cell-free extracts revealed that the resistant mutants were unable to catalyze a reaction between 2,6-diaminopurine and 5-phosphoribosyl-1-pyrophosphate to form the corresponding nucleotide. Adenylic pyrophosphorylase activity in the extracts of dap- r-6 was the same as in LT-2, but was greatly reduced in dap- r-3. The inosinic, guanylic, and xanthylic pyrophosphorylase activities were unaffected in both mutants. Possible mechanisms of resistance to 2,6-diaminopurine in the resistant mutants are discussed in light of the above observations.