Birkness K A, Swords W E, Huang P H, White E H, Dezzutti C S, Lal R B, Quinn F D
Division of AIDS, STD and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Infect Immun. 1999 Sep;67(9):4895-901. doi: 10.1128/IAI.67.9.4895-4901.1999.
Mycobacterium avium, the most common opportunistic pathogen in patients with AIDS, is frequently isolated from a variety of environmental sources, but rarely can these environmental isolates be epidemiologically linked with isolates known to cause human disease. Using a number of in vitro tissue culture assays, we found significant pathogenic differences between a serotype 4 human clinical M. avium isolate and a serotype 2 veterinary isolate. Cell association of the patient strain with a human intestinal cell line was 1.7 times that of the veterinary strain. Growth of this clinical strain in human peripheral blood mononuclear cell-derived macrophages increased from 12-fold higher than that of the veterinary isolate after 2 days to 200-fold higher after 4 days. By the conclusion of each experiment, lysis of all examined host cell types and accumulation of cell debris were observed in infections with the human isolate, but monolayers remained relatively intact in the presence of the animal isolate. The two strains also differed in the ability to stimulate human immunodeficiency virus replication in coinfected host cells, with p24 antigen levels after 6 days threefold higher in the cells coinfected with the clinical strain than in those infected with the veterinary strain. If the genetic differences responsible for the phenotypes observed in these assays can be identified and characterized, it may be possible to determine which M. avium strains in the environment are potential human pathogens.
鸟分枝杆菌是艾滋病患者中最常见的机会性致病菌,常从多种环境来源分离得到,但这些环境分离株很少能在流行病学上与已知引起人类疾病的分离株联系起来。通过一系列体外组织培养试验,我们发现血清型4的人源临床鸟分枝杆菌分离株与血清型2的兽源分离株之间存在显著的致病性差异。患者菌株与人肠道细胞系的细胞结合能力是兽源菌株的1.7倍。该临床菌株在人外周血单个核细胞衍生的巨噬细胞中的生长,从2天后比兽源分离株高12倍增加到4天后高200倍。在每个实验结束时,用人源分离株感染时观察到所有检测的宿主细胞类型均发生裂解且细胞碎片积累,但在存在动物分离株的情况下单层细胞仍相对完整。这两种菌株在共同感染的宿主细胞中刺激人类免疫缺陷病毒复制的能力也有所不同,共同感染临床菌株的细胞中6天后的p24抗原水平比感染兽源菌株的细胞高三倍。如果能够鉴定和表征导致这些试验中观察到的表型的基因差异,就有可能确定环境中的哪些鸟分枝杆菌菌株是潜在的人类病原体。