THE CONSEQUENCES OF MUTATION DURING THE GROWTH OF BIOCHEMICAL MUTANTS OF ESCHERICHIA COLI IV

Abstract

The restriction of the growth of histidine-independent bacteria by histidineless organisms was found, in unshaken and in aerated cultures, to be due to different causes. Yet in both instances there is the common principle that involves the modification of the medium by histidineless bacteria in the stationary phase. In aerated cultures, histidineless bacteria cease to grow when the histidine supply of the medium is exhausted, but they continue in the stationary stage to consume glucose until it too is absent from the medium. In the meantime the small number of histidine-independent back-mutants contained by histidineless cultures continue to grow. They are not influenced by the exhaustion of histidine from the medium but cease growth when the glucose is gone. The time of glucose disappearance, and hence the extent to which histidine-independent bacteria can undergo adaptive growth, depends upon the number of histidineless bacteria that are consuming glucose in the stationary stage. The number of histidineless bacteria is, in turn, a function of the initial concn. of histidine. For this reason, the adaptive growth of histidineless bacteria is greatest on low concns. of histidine and eventually does not take place as the histidine concn. becomes high enough. The rates of glucose utilization during growth in the stationary stage have been detd. and used to calculate the expected extents of adaptive growth and the expected composition of adapted cultures. The close correspondence of theory and expt. verifies the hypothesis. In unshaken cultures the adaptive growth of histidine-independent bacteria is regulated in a similar fashion. The glucose supply, however, does not become limiting. Rather, the histidineless bacteria in the stationary phase produce acid and an inhibitor (or inhibitors) which limit the amount of growth that is possible at any pH. This modification of the medium also occurs as a function of the number of histidineless bacteria and is responsible for the differences in the restriction of the adaptive growth of histidine-independent bacteria on different concns. of histidine.