Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system
Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system
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DOI：
10.1096/fj.09-132407
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发表时间：
2009-12-01
期刊：
影响因子：
4.8
通讯作者：
Schoolnik, Gary K.
中科院分区：
文献类型：
--
作者：
Alberto Flores-Valdez, Mario;Morris, Rowan P.;Schoolnik, Gary K.
细菌物种利用大量的表面结构与周围环境相互作用，并根据特定的刺激采用许多策略来重新配置细胞包膜。以链霉菌和芽孢杆菌为代表的革兰氏阳性细菌，通过渗透输入寡肽信号来控制一些暴露分子的产生(Opp)。这些寡肽调节细胞内的信号通路。在这项工作中，我们对人类病原体结核分枝杆菌(Mtb)的一个OPP进行了功能表征，并提出了它的重新注释。利用全基因组转录图谱，我们发现Opp需要调节几个基因的表达(折叠变化范围从-3.5到2.0)，其中大多数编码表面暴露的分子。这些包括与毒力相关的脂类、霉菌酸和二硫代甘油酸酯(PDIMs)以及PE家族蛋白。通过薄层层析和MALDI-TOF-MS，我们证实了脂类的变化，包括三酰甘油酯的变化积累和影响霉菌酸与PDIMs的比率。OPP功能缺失突变体在体外没有表现出生长缺陷，但在慢性感染期间减轻了负担，与WT Mtb感染相比，动物的死亡时间略有延迟。-Flores-Valdez，M.A.，Morris，R.P.，Laval，F.，Daffe，M.，Schoolnik，G.K.结核分枝杆菌通过寡肽渗透酶(Opp)运输系统调节其细胞表面。FASE B J.23,4091-4104(2009)。Www.fasebj.org
Bacterial species utilize a vast repertoire of surface structures to interact with their surroundings and employ a number of strategies to reconfigure the cellular envelope according to specific stimuli. Gram-positive bacteria, exemplified by Streptomyces and Bacillus species, control production of some exposed molecules by importing oligopeptide signals via permeases (Opp). Such oligopeptides modulate intracellular signaling pathways. In this work, we functionally characterized an Opp of the human pathogen Mycobacterium tuberculosis (Mtb) and propose its reannotation. Using genome-wide transcriptional profiling, we found that Opp was required to modulate (fold-change ranging from -3.5 to 2.0) the expression of several genes, most of them encoding surface-exposed molecules. These included the virulence-associated lipids mycolic acids and phthiocerol dimycocerosates (PDIMs) as well as PE-family proteins. By thin-layer chromatography and MALDI-TOF-MS we confirmed changes in the lipid profile, including an altered accumulation of triacylglycerides and an affected ratio of mycolic acids to PDIMs. An Opp loss of function mutant showed no in vitro growth defect, but had diminished burden during chronic infection and produced a slightly delayed time to death of animals when compared to WT Mtb infection.-Flores-Valdez, M. A., Morris, R. P., Laval, F., Daffe, M., Schoolnik, G. K. Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system. FASEB J. 23, 4091-4104 (2009). www.fasebj.org