Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection
Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection
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DOI：
10.1128/iai.67.9.4700-4707.1999
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发表时间：
1999-09-01
影响因子：
3.1
通讯作者：
Lyons, CR
中科院分区：
文献类型：
--
作者：
Byrd, TF;Lyons, CR
建立感染后在宿主中持续存在的能力是分枝杆菌的重要毒力决定因素，分枝杆菌是一种快速生长的分枝杆菌属物种，其在人类中引起多种临床综合征。我们已经获得了一个粗糙的，野生型人类临床分离的M。黑腹叶蜂M. A. M. S-S），其自发地从临床分离株分离。我们发现这很糟糕。与M.为了理解这种差异的基础，我们描述了这些变体在人类组织培养感染模型中的行为。III，M-R能够在人单核细胞中持续存在和增殖，而M. S-S缺乏这种能力。这两种变体都被人单核细胞吞噬。A1，A2，A3，A4，A5，A6，A7，A8，A9，A10，A11，相比之下，A1，A2，A3，A4，A5，A6，A7，A8，A9，A10，A11，A1两个M.在最近描述的成纤维细胞-分枝杆菌微菌落试验中，M结核和M.该菌株的生长特性与先前报道的无毒M.结核在单核细胞感染试验和小鼠肺部感染模型中，在Al. acidessus-R感染部位出现大量感染的单核吞噬细胞聚集体，但在M. S感染。我们的结论是M.该变异体改变了该生物体在宿主细胞中持续存在和繁殖的能力，这可能与我们在组织培养感染模型中观察到的表型变化有关。
The ability to persist in the host after the establishment of infection is an important virulence determinant for mycobacteria, Mycobacterium abscessus is a rapidly growing mycobacterial species which causes a variety of clinical syndromes in humans. We have obtained a rough, wild-type human clinical isolate of M. abscessus (M. abscessus-R) and a smooth, attenuated mutant (M. abscessus-S) which spontaneously dissociated from the clinical isolate. We have found that ill. abscessus-R is able to persist and multiply in a murine pulmonary infection model in contrast to M. abscessus-S, which is rapidly cleared, To understand the basis for this difference, we characterized the behavior of these variants in human tissue culture models of infection. ill, abscessus-R is able to persist and multiply in human monocytes, while M. abscessus-S is deficient in this ability. Both of these variants are phagocytized by human monocytes, Al, abscessus-R resides in a phagosome typical for pathogenic mycobacteria with a tightly adherent phagosomal membrane. In contrast, Al, abscessus-S resides in a "loose" phagosome with the phagosomal membrane separated from the bacterial cell wall. Both M. abscessus variants also have distinctive growth patterns in a recently described fibroblast-mycobacterium microcolony assay, with M, abscessus-R exhibiting growth characteristics similar to those previously reported for virulent M. tuberculosis and M. abscessus-S exhibiting growth characteristics similar to those previously reported for avirulent M. tuberculosis. In both the monocyte infection assay and the murine pulmonary infection model, numerous infected mononuclear phagocyte aggregates develop at sites of Al. abscessus-R infection, but are absent with M. abscessus-S infection. We conclude that a mutation has occurred in the M. abscessus-S variant which has altered the ability of this organism to persist and multiply in host cells and that this may be related to the phenotypic changes we have observed in our tissue culture models of infection.