Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia.
Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia.
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DOI：
10.1371/journal.pone.0008614
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发表时间：
2010-01-07
期刊：
影响因子：
3.7
通讯作者：
Cook GM
中科院分区：
文献类型：
--
作者：
Berney M;Cook GM
分枝杆菌是一组专性需氧菌，需要氧气生长，但矛盾的是，有能力在缺氧条件下生存和代谢。负责这种代谢可塑性的机制尚不清楚。在这里，我们报告的适应耻垢分枝杆菌缓慢的生长速度和缺氧使用碳限制连续培养。当M.当在50%的恒定氧饱和度下将smegestrin从4.6小时的倍增时间转换为69小时的倍增时间时，细胞通过呼吸链组分和F1 Fo-ATP合酶的下调来响应，这与细胞在降低的生长速率下对能量的较低需求一致。这是由分子机制的上调，允许更有效的能量产生（即复合物I）和使用替代的电子供体（例如氢化酶和初级脱氢酶），以保持在严重的能量限制条件下的电子传递链的还原当量的流动。氢化酶突变体显示出40%的生长产量减少，突出了这种酶在适应低能量供应的重要性。缓慢生长的细胞在50%的氧饱和度缺氧（0.6%的氧饱和度）的反应，通过开关氧清除细胞色素bd，质子转运细胞色素bc 1-aa 3超复合物，另一个假定的氢化酶，并取代NAD+依赖的酶与铁氧还蛋白依赖的酶，从而突出了一个新的模式分枝杆菌适应缺氧。铁氧化还原蛋白和氢化酶的表达提供了一个潜在的管道，在没有外源电子受体的情况下处理和转移电子。铁氧还蛋白依赖性酶的使用将允许细胞通过其中心碳代谢维持高的碳通量，而不依赖于NAD+/NADH比率。这些数据表明，分枝杆菌细胞的代谢可塑性显着，并提供了一个新的框架，了解他们的生存能力，在低能量条件和缺氧。
Mycobacteria are a group of obligate aerobes that require oxygen for growth, but paradoxically have the ability to survive and metabolize under hypoxia. The mechanisms responsible for this metabolic plasticity are unknown. Here, we report on the adaptation of Mycobacterium smegmatis to slow growth rate and hypoxia using carbon-limited continuous culture. When M. smegmatis is switched from a 4.6 h to a 69 h doubling time at a constant oxygen saturation of 50%, the cells respond through the down regulation of respiratory chain components and the F1Fo-ATP synthase, consistent with the cells lower demand for energy at a reduced growth rate. This was paralleled by an up regulation of molecular machinery that allowed more efficient energy generation (i.e. Complex I) and the use of alternative electron donors (e.g. hydrogenases and primary dehydrogenases) to maintain the flow of reducing equivalents to the electron transport chain during conditions of severe energy limitation. A hydrogenase mutant showed a 40% reduction in growth yield highlighting the importance of this enzyme in adaptation to low energy supply. Slow growing cells at 50% oxygen saturation subjected to hypoxia (0.6% oxygen saturation) responded by switching on oxygen scavenging cytochrome bd, proton-translocating cytochrome bc1-aa3 supercomplex, another putative hydrogenase, and by substituting NAD+-dependent enzymes with ferredoxin-dependent enzymes thus highlighting a new pattern of mycobacterial adaptation to hypoxia. The expression of ferredoxins and a hydrogenase provides a potential conduit for disposing of and transferring electrons in the absence of exogenous electron acceptors. The use of ferredoxin-dependent enzymes would allow the cell to maintain a high carbon flux through its central carbon metabolism independent of the NAD+/NADH ratio. These data demonstrate the remarkable metabolic plasticity of the mycobacterial cell and provide a new framework for understanding their ability to survive under low energy conditions and hypoxia.
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DOI：
10.1007/s10482-007-9215-x
发表时间：
2008-05-01
影响因子：
2.6
作者：
da Silva, Sofia M.;Venceslau, Sofia S.;Pereira, Ines A. C.
通讯作者：
Pereira, Ines A. C.
影响因子：
56.9
作者：
Olson, JW;Maier, RJ
通讯作者：
Maier, RJ
影响因子：
3.2
作者：
Beste, D. J. V.;Laing, E.;McFadden, J. J.
通讯作者：
McFadden, J. J.
影响因子：
11.4
作者：
Brekasis, D;Paget, MSB
通讯作者：
Paget, MSB
影响因子：
3.1
作者：
Fontan, Patricia;Aris, Virginie;Smith, Issar
通讯作者：
Smith, Issar