Subinhibitory cerulenin inhibits staphylococcal exoprotein production by blocking transcription rather than by blocking secretion
Subinhibitory cerulenin inhibits staphylococcal exoprotein production by blocking transcription rather than by blocking secretion
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DOI：
10.1099/mic.0.28102-0
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发表时间：
2005-09-01
期刊：
影响因子：
2.8
通讯作者：
Novick, RP
中科院分区：
文献类型：
--
作者：
Adhikari, RP;Novick, RP
浅蓝菌素是一种抗生素，通过共价修饰β-酮脂酰基-酰基载体蛋白合酶的链延长亚型的活性巯基来抑制脂肪酸合成。它还抑制其他利用必需硫醇的过程。浅蓝菌素已被广泛报道在亚MIC水平下阻断蛋白质分泌，这种作用被认为是通过干扰正常脂肪酸合成来干扰膜功能。本研究证实了低浓度抗生素引起的胞外蛋白质的显著减少，并通过北方印迹杂交表明，这种减少是由于干扰转录。通过在被浅蓝菌素抑制的基因entB和不被浅蓝菌素抑制的基因entA之间交换启动子，还表明抗生素不阻断分泌。浅蓝菌素的亚抑制浓度也被发现阻断至少两个调节因子agr和sae的转录激活，这两个因子通过信号转导发挥作用。干扰这些和其他监管决定因素的激活可能占了很大一部分的抑制作用，外蛋白生产的亚MIC浓度的浅蓝菌素。
Cerulenin is an antibiotic that inhibits fatty acid synthesis by covalent modification of the active thiol of the chain-elongation subtypes of beta-ketoacyl-acyl carrier protein synthase. It also inhibits other processes that utilize essential thiols. Cerulenin has been widely reported to block protein secretion at sub-MIC levels, an effect that has been postulated to represent interference with membrane function through interference with normal fatty acid synthesis. This study confirms the profound reduction in extracellular proteins caused by low concentrations of the antibiotic, and shows by Northern blot hybridization that this reduction is due to interference with transcription. By exchanging promoters between entB, a gene that is inhibited by cerulenin, and entA, a gene that is not, it was also shown that the antibiotic does not block secretion. Subinhibitory concentrations of cerulenin were also found to block transcriptional activation of at least two regulatory determinants, agr and sae, that function by signal transcluction. Interference with the activation of these and other regulatory determinants probably accounts for much of the inhibitory effect on exoprotein production of sub-MIC concentrations of cerulenin.