CcpA regulation of aerobic and respiration growth in Lactococcus lactis
CcpA regulation of aerobic and respiration growth in Lactococcus lactis
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DOI：
10.1046/j.1365-2958.2003.03700.x
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Gruss, A
中科院分区：
文献类型：
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作者：
Gaudu, P;Lamberet, G;Gruss, A
分解代谢控制蛋白CcpA是革兰氏阳性菌中高度保守的碳代谢调节因子。我们最近发现，乳酸乳球菌，在链球菌科的发酵细菌，是能够呼吸的生长后期时，血红素添加到通气的文化。由于呼吸的开始与培养基中葡萄糖的消耗同时发生，我们假设CcpA参与了这种代谢转换，并研究了它在通气和呼吸条件下在乳球菌生长中的作用。与发酵生长中观察到的适度变化相比，ccpA的失活将代谢转移到通气条件下的混合酸发酵。这种转变是由于通过NADH氧化酶的去阻遏改变了氧化还原平衡，从而消除了氧气并减少了NADH库。CcpA在呼吸代谢中也起着决定性的作用。向停滞期ccpA细胞添加血红素会导致生长停滞和细胞死亡。毒性是由于氧化应激引起的早熟血红素摄取。我们确定了血红素转运系统的阻遏物，并表明它是CcpA激活的目标。我们认为，CcpA介导的血红素摄取抑制是一种防止氧化损伤的指数增长开始的手段。因此，CcpA似乎控制着一个协调氧、铁和碳代谢的调节网络。
The catabolic control protein CcpA is the highly conserved regulator of carbon metabolism in Gram-positive bacteria. We recently showed that Lactococcus lactis, a fermenting bacterium in the family of Streptococcaceae, is capable of respiration late in growth when haem is added to aerated cultures. As the start of respiration coincides with glucose depletion from the medium, we hypothesized that CcpA is involved in this metabolic switch and investigated its role in lactococcal growth under aeration and respiration conditions. Compared with modest changes observed in fermentation growth, inactivation of ccpA shifts metabolism to mixed acid fermentation under aeration conditions. This shift is due to a modification of the redox balance via derepression of NADH oxidase, which eliminates oxygen and decreases the NADH pool. CcpA also plays a decisive role in respiration metabolism. Haem addition to lag phase ccpA cells results in growth arrest and cell mortality. Toxicity is due to oxidative stress provoked by precocious haem uptake. We identify the repressor of the haem transport system and show that it is a target of CcpA activation. We propose that CcpA-mediated repression of haem uptake is a means of preventing oxidative damage at the start of exponential growth. CcpA thus appears to govern a regulatory network that coordinates oxygen, iron and carbon metabolism.