Intracellular Replication of Mycobacterium marinum within Dictyostelium discoideum: Efficient Replication in the Absence of Host Coronin
Intracellular Replication of Mycobacterium marinum within Dictyostelium discoideum: Efficient Replication in the Absence of Host Coronin
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DOI：
10.1128/iai.71.6.3578-3586.2003
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发表时间：
2003-06
影响因子：
3.1
通讯作者：
J. Solomon;G. Leung;R. Isberg
中科院分区：
文献类型：
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作者：
J. Solomon;G. Leung;R. Isberg
摘要：海洋分枝杆菌会在鱼类和两栖动物中引起类似结核病的疾病，并且由于其快速生长和相对于其他分枝杆菌物种而言不太严格的遏制要求，已被用作模型分枝杆菌物种。我们在此证明，海分枝杆菌在盘基网柄菌细胞内生长，从而可以对可能调节分枝杆菌物种复制的宿主因子进行遗传分析。海分枝杆菌的细胞内生长模拟了先前观察到的培养吞噬细胞内生长的特性。一种在吞噬细胞内生长有缺陷的确定的细菌突变体被证明在盘状 D. discoideum 内也有类似的生长缺陷。为了测试宿主 Coronin 的作用（之前假设宿主 Coronin 可以积极调节小鼠巨噬细胞内的分枝杆菌生长），对一种确定的盘状 D. discoideum Coronin 突变体进行了分析。令人惊讶的是，相对于对照野生型菌株，Coronin的缺乏导致海分枝杆菌的细胞内复制增强。与之前的观察结果一致，一些吞噬体显示出冠状蛋白在隔室表面上的持久性，但蛋白质的共定位远不均匀。我们得出结论，在盘状 D. discoideum 中，除 Coronin 之外的其他因子也支持 M. marinum 的细胞内复制。
ABSTRACT Mycobacterium marinum causes tuberculosis-like disease in fish and amphibians and has been used as a model mycobacterial species because of its rapid growth and less stringent containment requirements relative to other mycobacterial species. We demonstrate here that M. marinum grows within Dictyostelium discoideum cells, allowing the genetic analysis of host factors that may modulate the replication of mycobacterial species. Intracellular growth of M. marinum was shown to mimic the properties previously observed for growth within cultured phagocytes. A defined bacterial mutant defective for growth within phagocytic cells was shown to be similarly defective for growth within D. discoideum. To test the role of host coronin, which was previously hypothesized to positively modulate mycobacterial growth within mouse macrophages, a defined D. discoideum coronin mutant was analyzed. Surprisingly, the absence of coronin resulted in enhanced intracellular replication of M. marinum relative to the control wild-type strain. Consistent with previous observations, some phagosomes showed persistence of coronin about the surface of the compartment, but colocalization of the protein was far from uniform. We conclude that in D. discoideum factors other than coronin support intracellular replication of M. marinum.