The Agr Quorum Sensing System Represses Persister Formation through Regulation of Phenol Soluble Modulins in Staphylococcus aureus.
The Agr Quorum Sensing System Represses Persister Formation through Regulation of Phenol Soluble Modulins in Staphylococcus aureus.
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Agr 群体感应系统通过调节金黄色葡萄球菌中的酚溶性调节蛋白来抑制持久性形成
DOI：
10.3389/fmicb.2017.02189
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发表时间：
2017
影响因子：
5.2
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Xu T;Wang XY;Cui P;Zhang YM;Zhang WH;Zhang Y
机会致病菌金黄色葡萄球菌已成为对公共卫生日益严重的威胁。而Agr群体感应（QS）系统是S.金黄色葡萄球菌的毒力，其功能障碍已被频繁报道，以促进菌血症和死亡率在临床感染。在这里，我们表明，Agr系统参与了持续性的形成在S。金黄色。无论是agrCA或agrD，但不是RNAIII的突变导致增加持久形成的稳定期文化。RNA-seq分析表明，在稳定期，AgrCA/AgrD和RNAIII突变体表现出一致的毒力相关基因（lip和splE等）上调。以及代谢基因（bioA和nanK等）的下调。同时，敲除agrCA或agrD可显著抑制pmt操纵子中的酚可溶性调节蛋白（psmα1-4，psmβ1-2）和酚可溶性调节蛋白（PSM）转运蛋白基因的表达，而RNA Ⅲ的突变可增强这些基因的表达。我们进一步发现，敲除psmα1-4或psmβ1-2可增加持续性形成，PSMαs和PSMβs的共过表达可逆转AgrCA突变对持续性形成的影响。我们还检测了代谢基因（arcA、hutU、narG、nanK等）的突变对持续存在形成的影响。可能会受到Agr系统的监管。发现ManNAc激酶编码基因nanK的缺失减少了持久性形成。综上所述，这些结果揭示了PSM依赖的Agr系统在持久性形成中的调节作用，并可能对MRSA持续性感染的临床治疗产生影响。
The opportunistic pathogen Staphylococcus aureus has become an increasing threat to public health. While the Agr quorum sensing (QS) system is a master regulator of S. aureus virulence, its dysfunction has been frequently reported to promote bacteremia and mortality in clinical infections. Here we show that the Agr system is involved in persister formation in S. aureus. Mutation of either agrCA or agrD but not RNAIII resulted in increased persister formation of stationary phase cultures. RNA-seq analysis showed that in stationary phase AgrCA/AgrD and RNAIII mutants showed consistent up-regulation of virulence associated genes (lip and splE, etc.) and down-regulation of metabolism genes (bioA and nanK, etc.). Meanwhile, though knockout of agrCA or agrD strongly repressed expression of phenol soluble modulin encoding genes psmα1-4, psmβ1-2 and phenol soluble modulins (PSM) transporter encoding genes in the pmt operon, mutation of RNAIII enhanced expression of the genes. We further found that knockout of psmα1-4 or psmβ1-2 augmented persister formation and that co-overexpression of PSMαs and PSMβs reversed the effects of AgrCA mutation on persister formation. We also detected the effects on persister formation by mutations of metabolism genes (arcA, hutU, narG, nanK, etc.) that are potentially regulated by Agr system. It was found that deletion of the ManNAc kinase encoding gene nanK decreased persister formation. Taken together, these results shed new light on the PSM dependent regulatory role of Agr system in persister formation and may have implications for clinical treatment of MRSA persistent infections.
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影响因子：
30.3
作者：
Cohen NR;Lobritz MA;Collins JJ
通讯作者：
Collins JJ
影响因子：
3.5
作者：
Atshan, Salman Sahab;Shamsudin, Mariana Nor;Ghaznavi-Rad, Ehsanollah
通讯作者：
Ghaznavi-Rad, Ehsanollah
DOI：
10.3390/s130405130
发表时间：
2013-04-18
期刊：
Sensors (Basel, Switzerland)
影响因子：
--
作者：
Gray B;Hall P;Gresham H
通讯作者：
Gresham H
影响因子：
3.7
作者：
Han J;He L;Shi W;Xu X;Wang S;Zhang S;Zhang Y
通讯作者：
Zhang Y
影响因子：
2.6
作者：
Bae, T;Schneewind, O
通讯作者：
Schneewind, O