Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock.
J Infect Dis. 2013 Dec 1;208(11):1841-8. doi: 10.1093/infdis/jit367. Epub 2013 Jul 30.
Staphylococcus aureus produces numerous virulence factors but little is known about their in vivo regulation during an infection.
The production of capsule and α-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.
In vitro analyses showed that capsule was positively regulated by MgrA, Agr, Sae, ArlR, and ClpC, and negatively by CodY and SbcDC. The α-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.
Our results suggest that, in vitro, Agr is the most important regulator for capsule and α-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 α-toxin, whereas saeR expression correlates best with hla expression.
金黄色葡萄球菌产生许多毒力因子，但对其在感染过程中的体内调节知之甚少。
通过比较 CYL11481（Newman 的衍生物）及其同源调控突变体在体外的差异，分析了荚膜和α-毒素的产生及其各自基因 cap5 和 hla 的表达。使用大鼠感染性心内膜炎模型进行了 cap5 和 hla 以及调节基因的体内表达时间分析。
体外分析表明，荚膜受 MgrA、Agr、Sae、ArlR 和 ClpC 的正调控，受 CodY 和 SbcDC 的负调控。α-毒素受 MgrA、Agr、Sae、ArlR 和 SbcDC 的正调控，受 ClpC 和 CodY 的负调控。体内分析表明，cap5 的表达与 mgrA 的表达相关性最好，而 hla 的表达与 sae 的表达相关性最好。mgrA 的突变大大降低了 cap5 的体内表达。
我们的结果表明，在体外，Agr 是荚膜和α-毒素产生以及 cap5 转录的最重要调节因子，但 SaeR 是 hla 转录的最关键调节因子。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 的表达与 hla 的表达相关性最好。
