Identification of cyclic AMP-regulated genes in Mycobacterium tuberculosis complex bacteria under low-oxygen conditions
Identification of cyclic AMP-regulated genes in Mycobacterium tuberculosis complex bacteria under low-oxygen conditions
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DOI：
10.1128/jb.187.8.2681-2692.2005
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发表时间：
2005-04-01
影响因子：
3.2
通讯作者：
McDonough, KA
中科院分区：
文献类型：
--
作者：
Gazdik, MA;McDonough, KA
结核分枝杆菌是结核病（TB）的病原体，尽管目前有治疗选择，但每年仍有约200万人死于结核病。需要更好地了解这种细菌的生物学，以更好地防治结核病。分枝结核分枝杆菌基因组编码多达15种腺苷酸环化酶，表明环AMP（cAMP）在分枝杆菌中具有重要但被忽视的作用。本研究探讨了外源性cAMP对在低氧与环境条件下生长的牛分枝杆菌BCG中蛋白表达的影响。针对每种大气条件检查了摇动培养物和浅置培养物。通过二维凝胶电泳，在每种条件下观察到蛋白质表达的不同cAMP依赖性变化。振荡低氧培养产生的变化最多（12），而站立的环境条件显示最少（2）。通过质谱法从BCG中鉴定出5种上调的蛋白质，Rv 1265、Rv 2971、GroEL 2、PE（-）PGRS 6a和苹果酸脱氢酶，并且在两种M中也显示出在mRNA水平上受cAMP调节。结核病H37 Rv和BCG。据我们所知，这些数据提供了第一个直接的证据，cAMP介导的基因调控结核分枝杆菌复杂。
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), which kills approximately 2 million people a year despite current treatment options. A greater understanding of the biology of this bacterium is needed to better combat TB disease. The M. tuberculosis genome encodes as many as 15 adenylate cyclases, suggesting that cyclic AMP (cAMP) has an important, yet overlooked, role in mycobacteria. This study examined the effect of exogenous cAMP on protein expression in Mycobacterium bovis BCG grown under hypoxic versus ambient conditions. Both shaking and shallow standing cultures were examined for each atmospheric condition. Different cAMP-dependent changes in protein expression were observed in each condition by two-dimensional gel electrophoresis. Shaking low-oxygen cultures produced the most changes (12), while standing ambient conditions showed the fewest (2). Five upregulated proteins, Rv1265, Rv2971, GroEL2, PE(-)PGRS6a, and malate dehydrogenase, were identified from BCG by mass spectrometry and were shown to also be regulated by cAMP at the mRNA level in both M. tuberculosis H37Rv and BCG. To our knowledge, these data provide the first direct evidence for cAMP-mediated gene regulation in TB complex mycobacteria.