Dynamics of submerged growth of Mycobacterium tuberculosis under aerobic and microaerophilic conditions.

When Mycobacterium tuberculosis is grown in detergent-containing medium under continous agitation, multiplication is known to follow a logarithmic mode. When the cultures are not continuously shaken, but only agitated a few times a week to resuspend the bacilli and permit turbidity to be measured, the net increase suggests an arithmetic growth mode. It is shown here that a single pulse of aeration of an unshaken submerged culture of M. tuberculosis causes an almost instantaneous acceleration of growth, followed rapidly by a cessation of growth. Whether or not the bacilli will subsequently resume growth depends on the bacillary population density of the cuture at the time of application of the pulse of aeration. If the bacilli are permitted to grow in the depths of Dubos Tween Albumin broth without any agitation, they exhibit net arithmetic growth and attain a maximal population density greater than is seen in cultures exposed to occasional pulses of aeration. By the use of isotopically labeled cells, it has been shown that replication occurs ar a logarithmic rate amoung the small proportion of the bacilli that remain suspended in nonagitated cultures. This replication is balanced by settling of cells, resulting in a net appearance of arithmetic multiplication. The cells that have settled into the sediment replicate at a very slow rate, if at all, but do retain their viability for 4 weeks or longer. This suggests a possible analogy to quiescent tubercle bacilli in vivo.