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。在这里我们报道金黄色葡萄球菌通过丙酮酸的生产来调节戊酸倍他米松（BV）（一种用于治疗特应性皮炎的抗炎药）的耐受性，从而调节三羧酸（TCA）循环。在5种不同的抗炎类固醇中，向培养基中添加BV或丙酸氯倍他索可延缓金黄色葡萄球菌的生长。通过RNA-seq进行的全面基因表达分析表明，BV增加了金黄色葡萄球菌糖酵解相关基因的表达。丙酮酸是糖酵解的产物，可抑制金黄色葡萄球菌BV抑制生长。在丙酮酸生物合成的TCA循环中加入草酰乙酸（一种化合物）也可以抑制BV的抑制作用。丙二酸酯是TCA周期中琥珀酸脱氢酶的抑制剂，可增加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调节TCA循环，从而提高了对抗炎类固醇BV的耐受性。