Cirillo J D, Falkow S, Tompkins L S, Bermudez L E
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center, San Francisco 94115, USA.
Infect Immun. 1997 Sep;65(9):3759-67. doi: 10.1128/iai.65.9.3759-3767.1997.
Environmental mycobacteria are a common cause of human infections. Recently, contaminated domestic water supplies have been suggested as a potential environmental source of several mycobacterial diseases. Since many of these mycobacterial species replicate best intracellularly, environmental hosts have been sought. In the present study, we examined the interaction of Mycobacterium avium with a potential protozoan host, the water-borne amoeba Acanthamoeba castellanii. We found that M. avium enters and replicates in A. castellanii. In addition, similar to that shown for mycobacteria within macrophages, M. avium inhibits lysosomal fusion and replicates in vacuoles that are tightly juxtaposed to the bacterial surfaces within amoebae. In order to determine whether growth of M. avium in amoebae plays a role in human infections, we tested the effects of this growth condition on virulence. We found that growth of M. avium in amoebae enhances both entry and intracellular replication compared to growth of bacteria in broth. Furthermore, amoeba-grown M. avium was also more virulent in the beige mouse model of infection. These data suggest a role for protozoa present in water environments as hosts for pathogenic mycobacteria, particularly M. avium.
环境分枝杆菌是人类感染的常见病因。最近,有人提出受污染的家庭供水可能是几种分枝杆菌病的潜在环境来源。由于这些分枝杆菌中的许多种类在细胞内复制最佳,因此一直在寻找环境宿主。在本研究中,我们检测了鸟分枝杆菌与一种潜在的原生动物宿主——水生变形虫卡氏棘阿米巴的相互作用。我们发现鸟分枝杆菌可进入卡氏棘阿米巴并在其中复制。此外,与巨噬细胞内的分枝杆菌情况类似,鸟分枝杆菌抑制溶酶体融合,并在与变形虫内细菌表面紧密相邻的液泡中复制。为了确定鸟分枝杆菌在变形虫中的生长是否在人类感染中起作用,我们测试了这种生长条件对毒力的影响。我们发现,与在肉汤中生长相比,鸟分枝杆菌在变形虫中的生长增强了其进入细胞和细胞内复制的能力。此外,在米色小鼠感染模型中,在变形虫中生长的鸟分枝杆菌也更具毒力。这些数据表明,水环境中的原生动物作为致病分枝杆菌尤其是鸟分枝杆菌的宿主发挥了作用。