Morphological features and signature gene response elicited by inactivation of FtsI in Mycobacterium tuberculosis
Morphological features and signature gene response elicited by inactivation of FtsI in Mycobacterium tuberculosis
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DOI：
10.1093/jac/dkn507
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发表时间：
2009-03-01
影响因子：
5.2
通讯作者：
Belisle, John T.
中科院分区：
文献类型：
--
作者：
Slayden, Richard A.;Belisle, John T.
细胞分裂中普遍保守的事件为开发针对结核分枝杆菌的新型化疗药物提供了机会。本研究的目的是使用β-内酰胺类抗菌剂头孢氨苄和哌拉西林抑制FtsI，并表征其形态变化和基因的全局转录活性，以确定FtsI失活的签名响应。头孢氨苄和哌拉西林用于阻断细胞分裂，并通过显微镜观察细菌形态和超微结构的影响。进行全局转录分析，以确定FtsI抑制对细胞周期过程的影响，并确定分子marker.Inhibition of FtsI with cefalexin and piperacillin leads in filamentous cells with multiple concentric ring and occasionally branching as visualized by light and electron microscopy.基于全基因组微阵列的转录谱分析和转录定位可以评估FtsI抑制后的细胞周期过程，并表征转录反应和细胞周期过程。结核因此，FtsI是药物发现的靶点，这些研究提供了FtsI失活的分子特征，可应用于新型FtsI抑制剂的筛选策略。
Universally conserved events in cell division provide the opportunity for the development of novel chemotherapeutics against Mycobacterium tuberculosis. The aim of this study was to use the beta-lactam antimicrobials cefalexin and piperacillin to inhibit FtsI and characterize the morphological changes and global transcriptional activities of genes to identify a signature response to FtsI inactivation.Cefalexin and piperacillin were used to block cell division, and microscopy was used to evaluate the effects on bacterial morphology and ultrastructure. Global transcriptional analysis was performed to determine the impact of FtsI inhibition on cell cycle processes and to identify molecular markers.Inhibition of FtsI with cefalexin and piperacillin resulted in filamentous cells with multiple concentric rings and occasional branching as visualized by light and electron microscopy. Whole genome microarray-based transcriptional profiling and transcriptional mapping allowed the evaluation of cell cycle processes in response to inhibition of FtsI and characterization of transcriptional response and cell cycle processes.This study substantiated that FtsZ-ring constriction and septal resolution require the transpeptidase activity of FtsI, making FtsI essential for cell division in M. tuberculosis. Therefore, FtsI is a target for drug discovery, and these studies provided a molecular signature of FtsI inactivation that can be applied to screening strategies for novel FtsI inhibitors.