Mutational and Phylogenetic Analyses of the Mycobacterial mbt Gene Cluster
Mutational and Phylogenetic Analyses of the Mycobacterial mbt Gene Cluster
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DOI：
10.1128/jb.05811-11
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发表时间：
2011-11-01
影响因子：
3.2
通讯作者：
Quadri, Luis E. N.
中科院分区：
文献类型：
--
作者：
Chavadi, Sivagami Sundaram;Stirrett, Karen L.;Quadri, Luis E. N.
分枝杆菌素铁载体系统存在于许多分枝杆菌属物种中，包括结核分枝杆菌和其他临床相关分枝杆菌。据信，该铁载体系统被致病性和非致病性分枝杆菌分别用于在体内和离体铁限制环境中获取铁。根据序列分析，已预测位于所谓的 mbt 基因簇中的几个结核分枝杆菌基因是分枝杆菌素核心支架生物合成所必需的。目前还缺乏系统的、受控的突变分析来探讨这些基因对于分枝杆菌素产生的假设本质。 mbt 基因簇直系同源物的保守程度也有待研究。在这项研究中，我们试图最终确定九个 mbt 基因中的每一个是否是分枝杆菌素生产所必需的，并检查其他细菌中与结核分枝杆菌 mbt 基因簇同源的基因簇的保守性。我们报告了耻垢分枝杆菌中发现的 mbt 基因簇直向同源物的系统突变分析。该突变分析表明，所研究的 9 个 mbt 基因中有 8 个对于分枝杆菌素的产生至关重要。我们的基因组挖掘和系统发育分析揭示了几种细菌物种中存在直系同源 mbt 基因簇。这些基因簇显示出源自复杂进化路径的显着组织差异，其中可能包括水平基因转移。总而言之，本文报告的发现增进了我们对与毒力相关的重要分枝杆菌次级代谢产物生物合成的遗传要求的理解。
The mycobactin siderophore system is present in many Mycobacterium species, including M. tuberculosis and other clinically relevant mycobacteria. This siderophore system is believed to be utilized by both pathogenic and nonpathogenic mycobacteria for iron acquisition in both in vivo and ex vivo iron-limiting environments, respectively. Several M. tuberculosis genes located in a so-called mbt gene cluster have been predicted to be required for the biosynthesis of the core scaffold of mycobactin based on sequence analysis. A systematic and controlled mutational analysis probing the hypothesized essential nature of each of these genes for mycobactin production has been lacking. The degree of conservation of mbt gene cluster orthologs remains to be investigated as well. In this study, we sought to conclusively establish whether each of nine mbt genes was required for mycobactin production and to examine the conservation of gene clusters orthologous to the M. tuberculosis mbt gene cluster in other bacteria. We report a systematic mutational analysis of the mbt gene cluster ortholog found in Mycobacterium smegmatis. This mutational analysis demonstrates that eight of the nine mbt genes investigated are essential for mycobactin production. Our genome mining and phylogenetic analyses reveal the presence of orthologous mbt gene clusters in several bacterial species. These gene clusters display significant organizational differences originating from an intricate evolutionary path that might have included horizontal gene transfers. Altogether, the findings reported herein advance our understanding of the genetic requirements for the biosynthesis of an important mycobacterial secondary metabolite with relevance to virulence.