MgrA Activates Expression of Capsule Genes, but Not the α-Toxin Gene in Experimental Staphylococcus aureus Endocarditis
MgrA Activates Expression of Capsule Genes, but Not the α-Toxin Gene in Experimental Staphylococcus aureus Endocarditis
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DOI：
10.1093/infdis/jit367
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发表时间：
2013-12-01
影响因子：
6.4
通讯作者：
Lee, Chia Y.
中科院分区：
文献类型：
--
作者：
Gupta, Ravi Kr;Alba, Jimena;Lee, Chia Y.
背景。金黄色葡萄球菌产生大量毒力因子，但人们对其感染期间的体内调节知之甚少。方法。通过在体外比较 CYL11481（Newman 的衍生物）及其同基因调节突变体，分析了荚膜和 α-毒素的产生以及它们各自的基因 cap5 和 hla 的表达。使用大鼠感染性心内膜炎模型进行cap5和hla及其调节基因的体内瞬时表达。结果。体外分析表明，胶囊受到 MgrA、Agr、Sae、ArlR 和 ClpC 的正向调节，而受到 CodY 和 SbcDC 的负向调节。 α-毒素受 MgrA、Agr、Sae、ArlR 和 SbcDC 正向调节，但受 ClpC 和 CodY 负向调节。体内分析表明，cap5 表达与 mgrA 表达相关性最佳，而 hla 表达与 sae 表达相关性最佳。 mgrA 突变显着降低了体内 cap5 的表达。结论。我们的结果表明，在体外，Agr 是荚膜和 α-毒素产生以及 cap5 转录最重要的调节因子，但 SaeR 是 hla 转录最关键的调节因子。然而，在体内，MgrA 是荚膜的主要转录调节因子，但不是 α-毒素，而 saeR 表达与 hla 表达相关性最好。
Background. Staphylococcus aureus produces numerous virulence factors but little is known about their in vivo regulation during an infection.Methods. The production of capsule and alpha-toxin, and the expression of their respective genes, cap5 and hla, were analyzed by comparing CYL11481 (derivative of Newman) and its isogenic regulatory mutants in vitro. The temporal expression of cap5 and hla and the regulatory genes in vivo was carried out using a rat infective endocarditis model.Results. In vitro analyses showed that capsule was positively regulated by MgrA, Agr, Sae, ArlR, and ClpC, and negatively by CodY and SbcDC. The alpha-toxin was positively regulated by MgrA, Agr, Sae, ArlR, and SbcDC but negatively by ClpC and CodY. In vivo analyses showed that cap5 expression correlated best with mgrA expression, whereas hla expression correlated best with sae expression. Mutation in mgrA drastically reduced cap5 expression in vivo.Conclusions. Our results suggest that, in vitro, Agr is the most important regulator for capsule and alpha-toxin production, as well as for cap5 transcription, but SaeR is the most critical for hla transcription. However, in vivo, MgrA is the major transcriptional regulator of capsule, but not alpha-toxin, whereas saeR expression correlates best with hla expression.