Identification of cell cycle regulators in Mycobacterium tuberculosis by inhibition of septum formation and global transcriptional analysis

Identification of cell cycle regulators in Mycobacterium tuberculosis by inhibition of septum formation and global transcriptional analysis
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DOI:
10.1099/mic.0.28762-0
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发表时间:
2006-06-01
期刊:
影响因子:
2.8
通讯作者:
Belisle, John T.
Belisle, John T.
中科院分区:
生物学4区
文献类型:
--
作者:
Slayden, Richard A.;Knudson, Dennis L.;Belisle, John T.

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在结核分枝杆菌中,隔膜形成和细胞分裂调控的机制仍不清楚。在其他细菌物种中,FtsZ聚合和隔膜形成除了受到转录调控外,还受到蛋白质相互作用的影响,这些因素的结合为这一过程提供了严格的调控。然而,已知影响FtsZ组装的蛋白同源物尚未在结核分枝杆菌中被鉴定和证实。这表明结核分枝杆菌可能具有调节隔膜形成的独特过程。为了开始解决这个知之甚少的结核分枝杆菌生理学方面,FtsZ抑制剂被用来阻止细胞分裂,并检查了对细菌形态和转录反应的影响。抑制隔膜形成阻止细胞分裂并导致细菌丝化。基于微阵列的转录谱分析可以评估对隔膜形成抑制的多种代谢过程,当与生物信息学相结合时,提供了一种识别可能影响隔膜形成的调控元件和其他基因产物的方法。
In Mycobacterium tuberculosis the mechanism of septum formation and regulation of cell division remains undefined. In other bacterial species FtsZ polymerization and septum formation are influenced through protein interactions in addition to transcriptional regulation, and the combination of these provides tight regulation of this process. However, homologues of proteins known to affect FtsZ assembly have not been identified and substantiated in M. tuberculosis. This suggests that M. tuberculosis may possess unique processes for regulation of septum formation. To begin to address this poorly understood aspect of M. tuberculosis physiology, FtsZ inhibitors were used to block cell division and the effects on bacterial morphology and the transcriptional response were examined. Inhibition of septum formation prevented cell division and led to bacterial filamentation. Microarray-based transcriptional profiling allowed the evaluation of multiple metabolic processes in response to inhibition of septum formation and when coupled with bioinformatics provided a means to identify regulatory elements and other gene products that probably influence septum formation.