DYNAMICS OF SUBMERGED GROWTH OF MYCOBACTERIUM-TUBERCULOSIS UNDER AEROBIC AND MICROAEROPHILIC CONDITIONS

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Abstract
When M. tuberculosis is grown in detergent-containing medium under continuous agitation, multiplication follows 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. 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 subsequently resume growth depends on the bacillary population density of the culture 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 was shown that replication occurs at a logarithmic rate among 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 settle into the sediment replicate at a very slow rate, if at all, but do retain their viability for 4 wk or longer. This suggests a possible analogy to quiescent tubercle bacilli in vivo.