Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp
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DOI：
10.1046/j.1365-2958.2000.01967.x
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发表时间：
2000-07-01
影响因子：
3.6
通讯作者：
Hughes, D
中科院分区：
文献类型：
--
作者：
Macvanin, M;Johanson, U;Hughes, D
鼠伤寒沙门菌抗氟西地酸EF-G突变体引起的生长率降低与平均细胞大小的增加密切相关。这是不寻常的，因为生长速度和细胞大小通常呈正相关。全球转录调节分子ppGpp在协调生长速率和分裂中起作用，其基础水平通常与分裂时细胞大小成反比。我们发现，耐富西地酸的EF-G突变体在稳态生长期间扰乱了ppGpp的基础水平，在饥饿期间扰乱了诱导水平。一个突变，fusA1，与最慢的生长速度和最大的细胞大小有关，导致ppGpp的基础水平降低到野生型菌株的三分之一。其他具有中等或野生型生长速率和细胞大小的fusA突变体ppGpp的基础水平正常或增加。体内ppGpp的基础水平与体外ppGpp对依赖突变体EF-G的翻译的抑制程度呈反比关系。突变体EF-G和ppGpp之间的相互作用增强与GTP的K-M增加相关。我们的研究结果表明，突变体EF-G通过RelA （PSI）途径调节ppGpp的产生。综上所述，耐氟西地酸的EF-G突变改变了ppGpp的水平，打破了细胞分裂时生长速度和细胞大小之间的正常关系。如果与这些突变相关的其他表型，如毒力丧失，也与通过改变转录模式影响的ppGpp水平的扰动有关，那就不足为奇了。
Reductions in growth rate caused by fusidic acid-resistant EF-G mutants in Salmonella typhimurium correlate strongly with increased mean cell size. This is unusual because growth rate and cell size normally correlate positively. The global transcription regulator molecule ppGpp has a role in co-ordinating growth rate and division, and its basal level normally correlates inversely with cell size at division. We show that fusidic acid-resistant EF-G mutants have perturbed ppGpp basal levels during steady-state growth and perturbed induced levels during starvation. One mutation, fusA1, associated with the slowest growth rate and largest cell size, causes a reduction in the basal level of ppGpp to one-third of that found in the wild-type strain. Other fusA mutants with intermediate or wild-type growth rates and cell sizes have either normal or increased basal levels of ppGpp. There is an inverse relationship between the basal level of ppGpp in vivo and the degree to which translation dependent on mutant EF-G is inhibited by ppGpp in vitro. This enhanced interaction between mutant EF-G and ppGpp correlates with an increased K-M for GTP. Our results suggest that mutant EF-G modulates the production of ppGpp by the RelA (PSI) pathway. In conclusion, fusidic acid-resistant EF-G mutations alter the level of ppGpp and break the normal relationship between growth rate and cell size at division. It would not be surprising if other phenotypes associated with these mutants, such as loss of virulence, were also related to perturbations in ppGpp levels effected through altered transcription patterns.