Mutations that confer resistance to 2-deoxyglucose reduce the specific activity of hexokinase from Myxococcus xanthus

The glucose analog 2-deoxyglucose (2dGlc) inhibits the growth and multicell ular development of Myxococcus xanthus. Mutants of M. xanthus resistant to 2dGlc, designated hex mutants, arise at a low spontaneous frequency. Expres sion of the Escherichia coli glk (glucokinase) gene in M. xanthus hex mutan ts restores 2dGlc sensitivity, suggesting that these mutants arise upon the loss of a soluble hexokinase function that phosphorylates 2dGlc to form th e toxic intermediate, 2-deoxyglucose-6-phosphate. Enzyme assays of M. xanth us extracts reveal a soluble hexokinase (ATP:D-hexose-6-phosphotransferase; EC 2.7.1.1) activity but no phosphotransferase system activities. The hex mutants have lower levels of hexokinase activities than the wild type, and the levels of hexokinase activity exhibited by the hex mutants are inversel y correlated with the ability of 2dGlc to inhibit their growth and sporulat ion. Both 2dGlc and N-acetylglucosamine act as inhibitors of glucose turnov er by the M. xanthus hexokinase in vitro, consistent with the finding that glucose and N-acetylglucosamine can antagonize the toxic effects of 2dGlc i n vivo.