6-diazo-5-oxo-l-norleucine Inhibition of Escherichia Coli.

Coggin, J. H., Jr. (The University of Chicago, Chicago, Ill.), and W. R. Martin. 6-Diazo-5-oxo-l-norleucine inhibition of Escherichia coli. J. Bacteriol. 89:1348-1353. 1965.-The glutamine analogue 6-diazo-5-oxo-l-norleucine (DON) induced filaments and spheroplasts in Escherichia coli during the transition of sensitive populations to a state of resistance. Resistance developed at a frequency suggesting mutant selection. The morphology of cells resistant to 100 mug of DON per ml was indistinguishable from that of sensitive cells. DON-resistant cells exhibited an extended growth lag when cultured in the absence of the drug. This extended lag could be reduced to the lag time of parent sensitive cells by a combination of d-glucosamine and inosine or by DON. Viable counts during the lag period of resistant cells indicate that this lag results from a decrease in the number of cells during the first 2 hr of incubation. A combination of d-glucosamine and inosine was required for complete prevention of the DON inhibition of sensitive cells. The results indicate that DON not only inhibits de novo purine biosynthesis but that it also prevents hexosamine synthesis and, ultimately, cell-wall synthesis in E. coli.