Yin Jianhua, Meng Qiu, Fu Huihui, Gao Haichun
Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Key Laboratory for Agro-Microbial Research and Utilization, Zhejiang Province Hangzhou, Zhejiang, 310058, China.
Sci Rep. 2016 Apr 14;6:24449. doi: 10.1038/srep24449.
Inhibition of bacterial growth under aerobic conditions by elevated levels of cyclic adenosine 3',5'-monophosphate (cAMP), first revealed more than 50 years ago, was attributed to accumulation of toxic methylglyoxal (MG). Here, we report a Crp-dependent mechanism rather than MG accumulation that accounts for the phenotype in Shewanella oneidensis, an emerging research model for the bacterial physiology. We show that a similar phenotype can be obtained by removing CpdA, a cAMP phosphodiesterase that appears more effective than its Escherichia coli counterpart. Although production of heme c and cytochromes c is correlated well with cAMP levels, neither is sufficient for the retarded growth. Quantities of overall cytochromes c increased substantially in the presence of elevated cAMP, a phenomenon resembling cells respiring on non-oxygen electron acceptors. In contrast, transcription of Crp-dependent genes encoding both cytochromes bd and cbb3 oxidases is substantially repressed under the same condition. Overall, our results suggest that cAMP of elevated levels drives cells into a low-energetic status, under which aerobic respiration is inhibited.
50多年前首次发现，环磷酸腺苷（cAMP）水平升高会在有氧条件下抑制细菌生长，这一现象被认为是由于有毒甲基乙二醛（MG）的积累所致。在此，我们报告了一种依赖于Crp的机制，而非MG积累，来解释希瓦氏菌（Shewanella oneidensis）中的这一表型，希瓦氏菌是一种新兴的细菌生理学研究模型。我们发现，通过去除CpdA（一种比其大肠杆菌对应物更有效的cAMP磷酸二酯酶）也可获得类似的表型。尽管血红素c和细胞色素c的产生与cAMP水平密切相关，但两者均不足以导致生长迟缓。在cAMP水平升高的情况下，细胞色素c的总量大幅增加，这一现象类似于细胞在非氧电子受体上进行呼吸作用。相反，在相同条件下，编码细胞色素bd和cbb3氧化酶的Crp依赖性基因的转录受到显著抑制。总体而言，我们的结果表明，高水平的cAMP会使细胞进入低能量状态，在此状态下有氧呼吸受到抑制。
