The domains of slow bacterial growth.

Commonly used culture systems, e.g., batch culture and the chemostat, work poorly for defining the behavior of slowly growing bacteria, i.e., cultures with mass doubling times, tD, longer than 10-12 h. This has slowed the process of understanding how bacteria behave at the longer tD's that embrace most of their existence. Culture systems are identified that give useful access to these longer doubling times. When these slow-growth systems are used with nutrient-limited populations, it is found that cellular concentrations of guanosine 5'-diphosphate 3'-diphosphate, the main effector of the stringent response, commence rising above basal levels at tD's longer than 12 h until, at a tD of 60-70 h, the level is reached that causes the interdiction of protein and ribosome synthesis characteristic of the response. The abrupt onset of the stringent response in eubacteria at a particular tD, corresponding to a specific rate of nutrient uptake, makes oft-used growth equations that do not account for this onset, e.g., those of Monod or Pirt, poor descriptors of slow growth. A serious imbalance between lateral and transverse wall formation rates which, unless corrected, would lead to abnormal cell division can be inferred to develop at tD's longer than 10-12 h. The necessary correction may be supplied by the effects of increased levels of guanosine 5'-diphosphate 3'-diphosphate on transverse wall synthesis.