金黄色葡萄球菌中丙酮酸触发的 TCA 循环调节促进了倍他米松戊酸酯的耐受性。
Pyruvate-triggered TCA cycle regulation in Staphylococcus aureus promotes tolerance to betamethasone valerate.
机构信息
Department of Microbiology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo, 204-8588, Japan.
Department of Microbiology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo, 204-8588, Japan.
出版信息
Biochem Biophys Res Commun. 2020 Jul 23;528(2):318-321. doi: 10.1016/j.bbrc.2020.05.035. Epub 2020 May 29.
Staphylococcus aureus is a resident skin bacterium involved in the exacerbation of atopic dermatitis. Here we report that S. aureus regulates the tricarboxylic acid (TCA) cycle via the production of pyruvate for tolerance to betamethasone valerate (BV), an anti-inflammatory drug used in the treatment of atopic dermatitis. The addition of BV or clobetasol propionate to the medium among 5 different anti-inflammatory steroids delayed the growth of S. aureus. Comprehensive gene expression analysis by RNA-seq revealed that BV increased the expression of genes related to glycolysis in S. aureus. Pyruvate, a product of glycolysis, suppressed the S. aureus growth inhibition by BV. The addition of oxaloacetate, a compound in the TCA cycle biosynthesized from pyruvate, was also suppressed the inhibitory effect of BV. Malonate, an inhibitor of succinate dehydrogenase in the TCA cycle, increased the inhibitory effect of BV on the growth of S. aureus. These findings suggest that S. aureus promotes tolerance to BV, an anti-inflammatory steroid, by regulating the TCA cycle via the production of pyruvate.
金黄色葡萄球菌是一种常驻皮肤细菌，参与特应性皮炎的恶化。在这里，我们报告金黄色葡萄球菌通过产生丙酮酸来调节三羧酸（TCA）循环，以耐受倍他米松戊酸酯（BV），BV 是一种用于治疗特应性皮炎的抗炎药物。在 5 种不同抗炎类固醇的培养基中添加 BV 或丙酸氯倍他索会延迟金黄色葡萄球菌的生长。通过 RNA-seq 进行的综合基因表达分析表明，BV 增加了金黄色葡萄球菌中与糖酵解相关的基因表达。糖酵解的产物丙酮酸抑制了 BV 对金黄色葡萄球菌的生长抑制作用。来自丙酮酸的 TCA 循环生物合成的化合物草酰乙酸的添加也抑制了 BV 的抑制作用。TCA 循环中的琥珀酸脱氢酶抑制剂丙二酸增加了 BV 对金黄色葡萄球菌生长的抑制作用。这些发现表明，金黄色葡萄球菌通过产生丙酮酸来调节 TCA 循环，从而促进对 BV（一种抗炎类固醇）的耐受性。
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