The Influence of Adverse Conditions upon the Respiratory Metabolism and Growth of Human Tubercle Bacilli

Abstract
By chemical methods and also by Warburg''s microrespiration apparatus, the influence of certain adverse conditions on respiration and growth of the H37 strain was studied. The organisms reduce their metabolism to a very low level after a few days of starvation. Even after many days, addition of adequate foodstuff restores respiration to its original level; also, growth capacity is not destroyed. This ability to reduce respiration to a low level with retention of respiratory and proliferative capacity is not a general property of bacteria, and is apparently one of the factors contributing to the hardiness of tubercle bacilli. In [image]/150 phosphate and lactate, H37 is practically unaffected by pH at 1.5-12.0. Higher molarity of lactic and phosphoric acids, e.g., [image]/15, is highly damaging to respiration. These 2 opposite effects are probably due to the relative impermeability of the bacillus. The question of intracellular or extracellular destruction of H37 by acid or base in the body is discussed. By manometric and chemical methods, lactic acid production by H37 from glucose was shown to be extremely slight. Manometric studies showed that the same low yields are obtained with glycerol, glycerophos-phate, arabinose, inositol and levulose, and in biological fluids like caseous material and serum. Anaerobic exposure on Long''s medium or under non-nutrient conditions leads to complete destruction of both respiratory and proliferative capacity in a few days. The tissue obtained by intraperitoneal injection of the lipoid of H37 into rabbits has a respiration twice as high as that of dog''s muscle. At the same time it forms large amounts of lactic acid anaerobically from glucose. The author''s data and those of others indicate that in the center of the tubercle (known to be avascular) a condition of complete O lack is reached when its radius reaches 0.075-0.35 mm. Under such circumstances the monocytes and bacilli in the central area would have to depend on some anaerobic mechanism for energy. The monocytes can produce lactic acid to provide the necessary energy, and might therefore survive. As shown by these exps., tubercle bacilli are unable to regain respiratory or proliferative capacity after anaerobiosis, and therefore might not survive. The possibility exists, therefore, that the tubercle can bring about cessation of growth or even eradication of tubercle bacilli by this mechanism.