Shaw Lindsey N, Jonsson Ing-Marie, Singh Vineet K, Tarkowski Andrej, Stewart George C
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
Infect Immun. 2007 Sep;75(9):4519-27. doi: 10.1128/IAI.00491-07. Epub 2007 Jun 4.
The success of Staphylococcus aureus as a pathogen can largely be attributed to the plethora of genetic regulators encoded within its genome that temporally regulate its arsenal of virulence determinants throughout its virulence lifestyle. Arguably the most important of these is the two-component, quorum-sensing system agr. Over the last decade, the controversial presence of a second quorum-sensing system (the TRAP system) has been proposed, and it has been mooted to function as the master regulator of virulence in S. aureus by modulating agr. Mutants defective in TRAP are reported to be devoid of agr expression, lacking in hemolytic activity, essentially deficient in the secretion of virulence determinants, and avirulent in infection models. A number of research groups have questioned the validity of the TRAP findings in recent years; however, a thorough and independent analysis of its role in S. aureus physiology and pathogenesis has not been forthcoming. Therefore, we have undertaken such an analysis of the TRAP locus of S. aureus. We found that a traP mutant was equally hemolytic as the wild-type strain. Furthermore, transcriptional profiling found no alterations in the traP mutant in expression levels of agr or in expression levels of multiple agr-regulated genes (hla, sspA, and spa). Analysis of secreted and surface proteins of the traP mutant revealed no deviation in comparison to the parent. Finally, analysis conducted using a murine model of S. aureus septic arthritis revealed that, in contrast to an agr mutant, the traP mutant was just as virulent as the wild-type strain.
金黄色葡萄球菌作为一种病原体的成功,很大程度上可归因于其基因组中编码的大量遗传调控因子,这些调控因子在其整个致病过程中对其毒力决定因素库进行适时调控。其中最重要的当属双组分群体感应系统agr。在过去十年中,有人提出存在第二种群体感应系统(TRAP系统),并且有人推测它通过调节agr来充当金黄色葡萄球菌毒力的主要调节因子。据报道,TRAP缺陷型突变体缺乏agr表达,缺乏溶血活性,在毒力决定因素的分泌方面基本存在缺陷,并且在感染模型中无致病性。近年来,一些研究小组对TRAP的研究结果的有效性提出了质疑;然而,尚未对其在金黄色葡萄球菌生理学和发病机制中的作用进行全面且独立的分析。因此,我们对金黄色葡萄球菌的TRAP基因座进行了这样的分析。我们发现,traP突变体与野生型菌株的溶血能力相同。此外,转录谱分析发现,traP突变体中agr的表达水平或多个agr调控基因(hla、sspA和spa)的表达水平均未发生改变。对traP突变体分泌蛋白和表面蛋白的分析表明,与亲本相比没有偏差。最后,使用金黄色葡萄球菌败血症性关节炎小鼠模型进行的分析表明,与agr突变体不同,traP突变体与野生型菌株的毒力相同。