DUBOS R J
J Exp Med. 1950 Oct 1;92(4):319-32. doi: 10.1084/jem.92.4.319.
The growth of tubercle bacilli in vitro was inhibited by the addition of the sodium salts of very low concentrations of certain organic acids to a variety of liquid and agar culture media containing whole serum or serum albumin. Capric acid was the most active of the compounds tested, but inhibition of growth occurred also with the shorter aliphatic acids. Lactic acid was also growth-inhibitory, whereas the keto and dicarboxylic acids tested were inactive in this respect. The inhibitory activity of the aliphatic acids and of lactic acid increased as the pH of the medium was lowered by addition of HCl. It was greater in media enriched with serum or with oleic acid-albumin complex, but was otherwise fairly independent of the composition of the medium. The inhibitory effect appears to be bacteriostatic rather than bactericidal and to depend upon a disturbance of the normal metabolic processes of the bacilli. Some of the long chain fatty acids caused a marked enhancement of growth when used in low concentrations and in admixture with enough serum albumin to overcome their toxicity. The significance of these findings is discussed with reference to the survival and multiplication of tubercle bacilli in vivo within inflammatory and caseous areas, which are known to be often acidic and to contain high concentrations of organic acids.
在含有全血清或血清白蛋白的多种液体和琼脂培养基中,加入极低浓度的某些有机酸钠盐后,结核杆菌的体外生长受到抑制。癸酸是所测试化合物中活性最强的,但较短链的脂肪酸也能抑制其生长。乳酸也具有生长抑制作用,而所测试的酮酸和二羧酸在这方面则无活性。通过添加盐酸降低培养基的pH值时,脂肪酸和乳酸的抑制活性会增强。在富含血清或油酸 - 白蛋白复合物的培养基中,这种抑制活性更强,但在其他方面,它与培养基的组成关系不大。这种抑制作用似乎是抑菌而非杀菌的,并且取决于对杆菌正常代谢过程的干扰。一些长链脂肪酸在低浓度下与足够的血清白蛋白混合使用以克服其毒性时,会显著促进生长。结合结核杆菌在体内炎症和干酪样区域中的存活和繁殖情况,对这些发现的意义进行了讨论,已知这些区域通常呈酸性且含有高浓度的有机酸。