Aureusimines in Staphylococcus aureus are not involved in virulence.
Aureusimines in Staphylococcus aureus are not involved in virulence.
复制标题
DOI：
10.1371/journal.pone.0015703
复制
发表时间：
2010-12-29
期刊：
影响因子：
3.7
通讯作者：
Bae T
中科院分区：
文献类型：
--
作者：
Sun F;Cho H;Jeong DW;Li C;He C;Bae T
最近，报道了二肽金亚胺激活葡萄球菌毒力基因的表达，如α-溶血素，并增加S。金黄色葡萄球菌毒力。令人惊讶的是，大多数受金霉素影响的毒力基因构成了SaeRS双组分系统（TCS）调节子的一部分，这增加了SaeRS可能直接或间接参与金霉素依赖性信号传导过程的可能性。使用HPLC分析，我们证实，一个转座子突变体的aureusimine二肽合成酶的基因编码的ausA，不产生二肽。然而，转座子突变体显示出正常的溶血活性和α-溶血素/SaeP生产。此外，P1启动子的sae操纵子，SaeRS TCS的目标之一，显示正常的转录活性。此外，与原始报告相反，ausA转座子突变体在动物感染模型中没有表现出减弱的毒力。DNA测序显示，在原始研究中使用的ausA缺失突变体在saeS中具有83 nt重复。原始突变体的溶血活性通过携带sae操纵子的质粒恢复。sae操纵子的突变体对氯霉素和红霉素表现出更高的抗性，这两种抗生素在葡萄球菌诱变过程中被广泛使用。在43°C下，在红霉素和通风的存在下，通常用于葡萄球菌诱变的条件，saeR转座子突变体比对照突变体生长得快得多，并且saeR突变体在混合培养实验中高度富集。我们的研究结果表明，先前报道的金黄色葡萄球菌的基因调控和毒力的作用是由于一个意想不到的突变saeS，这可能是由于选择的突变体对环境压力的抗性升高。因此，没有证据表明二肽金亚胺在sae介导的毒力因子产生中起作用或有助于葡萄球菌的毒力。
Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase S. aureus virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS), raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process. Using HPLC analyses, we confirmed that a transposon mutant of ausA, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the sae operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the ausA transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the ausA deletion mutant used in the original study has an 83 nt-duplication in saeS. Hemolysis activity of the original mutant was restored by a plasmid carrying the sae operon. A mutant of the sae operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an saeR transposon mutant grew much faster than a control mutant and the saeR mutant was highly enriched in a mixed culture experiment. Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in saeS, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in sae-mediated virulence factor production or contribute to staphylococcal virulence.
登录
查看更多内容
DOI：
10.1099/00221287-6-1-2-95
发表时间：
1952-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
DUTHIE, ES;LORENZ, LL
通讯作者：
LORENZ, LL
影响因子：
2.8
作者：
Giraudo, AT;Cheung, AL;Nagel, R
通讯作者：
Nagel, R
影响因子：
3.2
作者：
Geiger, Tobias;Goerke, Christiane;Wolz, Christiane
通讯作者：
Wolz, Christiane
DOI：
10.1073/pnas.0404728101
发表时间：
2004-08-17
影响因子：
11.1
作者：
Bae, T;Banger, AK;Missiakas, DM
通讯作者：
Missiakas, DM
影响因子：
2.6
作者：
Bae, T;Schneewind, O
通讯作者：
Schneewind, O