Global regulation of gene expression in response to cysteine availability in Clostridium perfringens.

Global regulation of gene expression in response to cysteine availability in Clostridium perfringens.
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DOI:
10.1186/1471-2180-10-234
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发表时间:
2010-09-07
期刊:
影响因子:
4.2
通讯作者:
Martin-Verstraete I
Martin-Verstraete I
中科院分区:
生物学3区
文献类型:
--
作者:
André G;Haudecoeur E;Monot M;Ohtani K;Shimizu T;Dupuy B;Martin-Verstraete I

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半胱氨酸在细胞生理学中起着至关重要的作用,由于其反应性,其合成受到严格的控制。然而,与其他细菌相比,梭状芽孢杆菌的硫代谢及其调控机制知之甚少。在产气荚膜梭菌中,双组分系统VirR/VIRS除了控制几个毒素基因的表达外,还控制着参与蛋氨酸到半胱氨酸转化的UBIG操纵子的表达。产气荚膜梭菌毒力调节基因与硫代谢之间的联系促使我们更详细地分析这种代谢。我们首先对产气荚膜梭菌的硫代谢进行了尝试性的重建,并将这些数据与菌株13在不同硫源存在下的生长相关联。令人惊讶的是,产气荚膜梭菌可以通过一种非典型的仍未确定的途径将半胱氨酸转化为蛋氨酸。我们进一步比较了菌株13在半胱氨酸或同型半胱氨酸存在下生长后的表达谱,这些半胱氨酸或同型半胱氨酸对应于半胱氨酸耗尽的条件。在差异表达的177个基因中,我们发现了与硫代谢有关的基因,这些基因通过半胱氨酸特异的T盒系统(cysK-cysE,cysP1和cysP2)或S盒核糖开关(metK和mett)提前终止转录。我们还表明,UBIG操纵子通过T-box系统受到半胱氨酸可获得性的三重调节,由VirR/VIRS系统通过VR-RNA和VirX调节RNA提交。此外,我们还发现,PFOA(theta毒素)、NAGL(编码透明质酸酶的五个基因之一)和参与维持细胞氧化还原状态的基因的表达随着半胱氨酸的可获得性而差异表达。最后,我们发现,半胱氨酸限制诱导了参与[Fe-S]团簇生物发生的基因和编码乳酸脱氢酶的乳酸脱氢酶基因的表达。这种厌氧细菌的几个细胞生理学关键功能受到半胱氨酸供应的影响。虽然大多数与硫代谢有关的基因都是通过提前终止转录来调节的,但在半胱氨酸饥饿过程中,其他仍未确定的调节机制参与了基因表达的诱导。
Cysteine has a crucial role in cellular physiology and its synthesis is tightly controlled due to its reactivity. However, little is known about the sulfur metabolism and its regulation in clostridia compared with other firmicutes. In Clostridium perfringens, the two-component system, VirR/VirS, controls the expression of the ubiG operon involved in methionine to cysteine conversion in addition to the expression of several toxin genes. The existence of links between the C. perfringens virulence regulon and sulfur metabolism prompted us to analyze this metabolism in more detail. We first performed a tentative reconstruction of sulfur metabolism in C. perfringens and correlated these data with the growth of strain 13 in the presence of various sulfur sources. Surprisingly, C. perfringens can convert cysteine to methionine by an atypical still uncharacterized pathway. We further compared the expression profiles of strain 13 after growth in the presence of cystine or homocysteine that corresponds to conditions of cysteine depletion. Among the 177 genes differentially expressed, we found genes involved in sulfur metabolism and controlled by premature termination of transcription via a cysteine specific T-box system (cysK-cysE, cysP1 and cysP2) or an S-box riboswitch (metK and metT). We also showed that the ubiG operon was submitted to a triple regulation by cysteine availability via a T-box system, by the VirR/VirS system via the VR-RNA and by the VirX regulatory RNA. In addition, we found that expression of pfoA (theta-toxin), nagL (one of the five genes encoding hyaluronidases) and genes involved in the maintenance of cell redox status was differentially expressed in response to cysteine availability. Finally, we showed that the expression of genes involved in [Fe-S] clusters biogenesis and of the ldh gene encoding the lactate dehydrogenase was induced during cysteine limitation. Several key functions for the cellular physiology of this anaerobic bacterium were controlled in response to cysteine availability. While most of the genes involved in sulfur metabolism are regulated by premature termination of transcription, other still uncharacterized mechanisms of regulation participated in the induction of gene expression during cysteine starvation.
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