Impact of the functional status of saeRS on in vivo phenotypes of Staphylococcus aureus sarA mutants.
Impact of the functional status of saeRS on in vivo phenotypes of Staphylococcus aureus sarA mutants.
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DOI：
10.1111/mmi.12629
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发表时间：
2014-06
影响因子：
3.6
通讯作者：
Smeltzer MS
中科院分区：
文献类型：
--
作者：
Beenken KE;Mrak LN;Zielinska AK;Atwood DN;Loughran AJ;Griffin LM;Matthews KA;Anthony AM;Spencer HJ;Skinner RA;Post GR;Lee CY;Smeltzer MS
我们利用USA300菌株LAC的衍生物研究了sarA和saeRS对蛋白酶产生影响的体内相关性。结果证实，saeRS或sarA突变在菌血症模型中可在相当程度上降低毒力。然而，虽然消除蛋白酶的产生恢复了sarA突变体的毒力，但对saeRS突变体的影响很小。此外，saeRS的组成激活（saeRSC）增强了LAC的毒力，并在很大程度上恢复了等基因sarA突变体的毒力。基于这些结果，结合我们对代表性毒力因子α毒素、蛋白A （Spa）和细胞外核酸酶的分析，我们提出了一个模型，其中saeRS突变体的衰减主要由这些因子的产生减少来定义，而saeRS的组成型激活增加了毒力，并逆转了sarA突变体的衰减，因为它导致这些因子的产生增加和蛋白酶介导的降解减少。这种调节平衡在导管相关感染的小鼠模型中也很明显，结果表明saeRS对核酸酶产生的影响在这些感染的早期阶段起着重要作用，部分被sarA突变体中增加的蛋白酶产生所抵消。
We investigated the in vivo relevance of the impact of sarA and saeRS on protease production using derivatives of the USA300 strain LAC. The results confirmed that mutation of saeRS or sarA reduces virulence in a bacteremia model to a comparable degree. However, while eliminating protease production restored virulence in the sarA mutant, it had little impact in the saeRS mutant. Additionally, constitutive activation of saeRS (saeRSC) enhanced the virulence of LAC and largely restored virulence in the isogenic sarA mutant. Based on these results, together with our analysis of the representative virulence factors alpha toxin, protein A (Spa), and extracellular nucleases, we propose a model in which the attenuation of saeRS mutants is defined primarily by decreased production of such factors, while constitutive activation of saeRS increases virulence, and reverses the attenuation of sarA mutants, because it results in both increased production and decreased protease-mediated degradation of these same factors. This regulatory balance was also apparent in a murine model of catheter-associated infection, with the results suggesting that the impact of saeRS on nuclease production plays an important role during the early stages of these infections that is partially offset by increased protease production in sarA mutants.
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DOI：
10.1074/jbc.m113.502039
发表时间：
2013-10-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chen C;Krishnan V;Macon K;Manne K;Narayana SV;Schneewind O
通讯作者：
Schneewind O
DOI：
10.1073/pnas.1109071108
发表时间：
2011-11-08
影响因子：
11.1
作者：
Lower, Steven K.;Lamlertthon, Supaporn;Fowler, Vance G., Jr.
通讯作者：
Fowler, Vance G., Jr.
影响因子：
3.1
作者：
Beenken, KE;Blevins, JS;Smeltzer, MS
通讯作者：
Smeltzer, MS
影响因子：
6.4
作者：
Hammer ND;Reniere ML;Cassat JE;Zhang Y;Hirsch AO;Indriati Hood M;Skaar EP
通讯作者：
Skaar EP
影响因子：
6.4
作者：
Kobayashi, Scott D.;Malachowa, Natalia;DeLeo, Frank R.
通讯作者：
DeLeo, Frank R.