Nitrosothiols in bacterial pathogens and pathogenesis.

Nitrosothiols in bacterial pathogens and pathogenesis.
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DOI:
10.1089/ars.2012.4767
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发表时间:
2013-01
影响因子:
6.6
通讯作者:
Jay R. Laver;Samantha McLean;Lesley A. H. Bowman;L. Harrison;R. Read;R. Poole
Jay R. Laver;Samantha McLean;Lesley A. H. Bowman;L. Harrison;R. Read;R. Poole
中科院分区:
生物学2区
文献类型:
--
作者:
Jay R. Laver;Samantha McLean;Lesley A. H. Bowman;L. Harrison;R. Read;R. Poole

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s -亚硝基硫醇(SNOs)的形成和降解是蛋白质翻译后修饰的重要机制,在生物学中普遍存在。这些过程在真核细胞中发挥着很好的特征作用,包括各种病理和与慢性疾病有关。我们对这些过程在致病菌和其他细菌中的作用知之甚少。从生长和转录研究中可以清楚地看出,细菌可以感知外源性SNOs并对其作出反应。这些反应在表型和机制上不同于细菌对一氧化氮(NO)和NO释放剂以及过氧亚硝酸盐的反应。小的sno,如s -亚硝基谷胱甘肽(GSNO),由细菌积累,结果是细胞内的s -亚硝基蛋白(“s -亚硝基蛋白质组”)可检测到。最近,人们对肠杆菌内源性SNO形成的条件进行了描述。细胞内蛋白形成一氧化氮的倾向可能受到与真核系统中发现的相同的选择性规则的限制,但也受到细菌独特的一氧化氮解毒系统的影响,例如肠杆菌中的黄血红蛋白Hmp和脑膜炎球菌的一氧化氮还原酶。此外,细菌对这些蛋白的表达影响着哺乳动物宿主中SNOs的形成。未来方向在哺乳动物宿主中,细菌感染期间特异性SNO事件的损害在涉及先天免疫和细胞内信号传导的蛋白质背景下引起了相当大的兴趣。在细菌中,已经报道了许多s -亚硝基硫醇降解机制(例如,GSNO还原酶);另一些则被认为是有效的,这是基于对哺乳动物同类的考虑。细菌,特别是病原体的亚硝基硫醇需要更深入的研究。
SIGNIFICANCE The formation and degradation of S-nitrosothiols (SNOs) are important mechanisms of post-translational protein modification and appear to be ubiquitous in biology. These processes play well-characterized roles in eukaryotic cells, including a variety of pathologies and in relation to chronic conditions. We know little of the roles of these processes in pathogenic and other bacteria. RECENT ADVANCES It is clear, mostly from growth and transcriptional studies, that bacteria sense and respond to exogenous SNOs. These responses are phenotypically and mechanistically distinct from the responses of bacteria to nitric oxide (NO) and NO-releasing agents, as well as peroxynitrite. Small SNOs, such as S-nitrosoglutathione (GSNO), are accumulated by bacteria with the result that intracellular S-nitrosoproteins (the 'S-nitrosoproteome') are detectable. Recently, conditions for endogenous SNO formation in enterobacteria have been described. CRITICAL ISSUES The propensity of intracellular proteins to form SNOs is presumably constrained by the same rules of selectivity that have been discovered in eukaryotic systems, but is also influenced by uniquely bacterial NO detoxification systems, exemplified by the flavohemoglobin Hmp in enterobacteria and NO reductase of meningococci. Furthermore, the bacterial expression of such proteins impacts upon the formation of SNOs in mammalian hosts. FUTURE DIRECTIONS The impairment during bacterial infections of specific SNO events in the mammalian host is of considerable interest in the context of proteins involved in innate immunity and intracellular signalling. In bacteria, numerous mechanisms of S-nitrosothiol degradation have been reported (e.g., GSNO reductase); others are thought to operate, based on consideration of their mammalian counterparts. The nitrosothiols of bacteria and particularly of pathogens warrant more intensive investigation.