Phenotypic variability of the sensitivity to cycloserine of Klebsiella aerogenes NCTC 418, growing in chemostat culture.

The susceptibility of Klebsiella aerogenes to cycloserine varied according to the growth conditions. In batch culture, cells were less susceptible to the antibiotic when glycine was present in the medium, presumably due to competition between glycine and cycloserine for the uptake system by which glycine, D-alanine and cycloserine are transported into the cell. In the chemostat at average dilution rates, ammonia-limited cultures were more susceptible to the antibiotic than were glucose-limited cultures. Under phosphate-limiting conditions cultures were at least ten times less susceptible. Under ammonia and phosphate limitation the susceptibility increased with increasing growth rate. The sensitivity of glucose-limited cells was independent of the growth rate. A high-affinity uptake system for cycloserine (as measured by D-alanine transport) was present in ammonia- and glucose-limited cells, but not in phosphate-limited cells. Thus, the phenotypically defined alterations in the susceptibility of the bacterium to cycloserine could be correlated with variations in its uptake system for the antibiotic.