Crowle A J, Tsang A Y, Vatter A E, May M H
J Clin Microbiol. 1986 Nov;24(5):812-21. doi: 10.1128/jcm.24.5.812-821.1986.
Mycobacterium avium is a cause of nontuberculous chronic granulomatous infections which is attracting increased attention as a frequent opportunistic pathogen in acquired immunodeficiency syndrome. Some important aspects of its human pathogenicity were investigated by using cultured human macrophages infected with it. The uptake and replication of various strains of M. avium in the macrophages could be measured by CFU counts of the bacteria in samples of lysed, sonicated macrophages. Microscopic counts of acid-fast bacilli were not useful because the bacteria multiplying in the macrophages were usually not acid fast. Electron microscopy showed the intracellular bacilli to multiply by transverse fission, to be surrounded in individual vacuoles by a broad electronlucent zone, and to have thinner cell walls than extracellularly grown M. avium. Fifteen strains, including examples of serovars 1, 2, 4, 8, and 9, were studied for uptake and rate of replication in cultured macrophages from three normal subjects. The strains were isolates from patients with nontuberculous granulomatous infection, acquired immunodeficiency syndrome, or unrelated problems, or they were laboratory reference cultures. There were no differences among them in phagocytosis, but there were differences in intracellular replication. Laboratory strains tended to be avirulent, that is, they did not replicate in the macrophages. Patient isolates usually were virulent and could be compared for virulence by intracellular replication rates. Virulence correlated with flat, transparent bacterial colony morphology on nutrient agar but not with serovar or kind of patient from whom the bacteria were isolated. However, among strains of transparent colony morphology there were wide differences in virulence. A virulent bacilli generally produced domed, opalescent colonies on nutrient agar. A virulent bacilli predominated in populations of M. avium conditioned to growth in bacteriologic culture medium. Bacilli of virulent colony morphology predominated in populations passaged through cultured macrophages. The model described here presents a new approach to the investigation of the pathogenicity of M. avium for human subjects and may be more patient relevant than animal models.
鸟分枝杆菌是引起非结核性慢性肉芽肿感染的病原体，作为获得性免疫缺陷综合征中常见的机会性致病菌，正受到越来越多的关注。通过使用感染该菌的培养人巨噬细胞，对其人类致病性的一些重要方面进行了研究。通过对裂解、超声处理的巨噬细胞样本中的细菌进行菌落形成单位（CFU）计数，可以测量不同菌株的鸟分枝杆菌在巨噬细胞中的摄取和复制情况。抗酸杆菌的显微镜计数并不有用，因为在巨噬细胞中繁殖的细菌通常不抗酸。电子显微镜显示，细胞内的杆菌通过横向分裂繁殖，被一个宽的电子透明区包围在单个液泡中，并且细胞壁比细胞外生长的鸟分枝杆菌更薄。研究了包括血清型1、2、4、8和9的菌株在内的15个菌株在来自三名正常受试者的培养巨噬细胞中的摄取和复制速率。这些菌株分离自患有非结核性肉芽肿感染、获得性免疫缺陷综合征或无关疾病的患者，或者是实验室参考培养物。它们在吞噬作用方面没有差异，但在细胞内复制方面存在差异。实验室菌株往往无毒，也就是说，它们不在巨噬细胞中复制。患者分离株通常有毒，可以通过细胞内复制速率比较毒力。毒力与营养琼脂上扁平、透明的细菌菌落形态相关，但与血清型或分离细菌的患者类型无关。然而，在透明菌落形态的菌株中，毒力存在很大差异。有毒力的杆菌通常在营养琼脂上产生圆顶状、乳白色的菌落。在适应细菌学培养基生长的鸟分枝杆菌群体中，有毒力的杆菌占主导。在通过培养巨噬细胞传代的群体中，具有毒力菌落形态的杆菌占主导。这里描述的模型为研究鸟分枝杆菌对人类受试者的致病性提供了一种新方法，可能比动物模型更与患者相关。
