saeRS and sarA act synergistically to repress protease production and promote biofilm formation in Staphylococcus aureus.
saeRS and sarA act synergistically to repress protease production and promote biofilm formation in Staphylococcus aureus.
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DOI：
10.1371/journal.pone.0038453
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Smeltzer MS
中科院分区：
文献类型：
--
作者：
Mrak LN;Zielinska AK;Beenken KE;Mrak IN;Atwood DN;Griffin LM;Lee CY;Smeltzer MS
葡萄球菌辅助调节因子（sarA）的突变限制了不同金黄色葡萄球菌菌株中生物膜的形成，但也有例外。其中之一是通常研究的菌株纽曼。该菌株有两个潜在相关的缺陷，第一个是阻止纤连蛋白结合蛋白FnbA和FnbB锚定到细胞壁的突变，第二个是saeS中的点突变，导致saePQRS调节系统的组成性激活。我们修复了这些缺陷，以确定是否在生物膜形成中起作用，如果是这样，这是否可以解释纽曼中sarA的影响减少。恢复表面锚定FnbA增强生物膜的形成，但突变的sarA在此fnbA阳性菌株增加，而不是减少生物膜的形成。纽曼的saeS修复衍生物（P18 L）或纽曼saeRS突变体（ΔsaeRS）中sarA的突变导致与临床分离株中观察到的相似的生物膜缺陷表型，即使在缺乏表面锚定的FnbA的情况下。与纽曼sarA突变体相比，这些表型与P18 L和ΔsaeRS sarA突变体中细胞外蛋白酶产生增加和FnbA和/或Spa积累减少相关。减少的积累的温泉被逆转的基因编码aureolysin的突变，而减少的积累的FnbA被逆转的sspABC操纵子的突变。这些结果表明，saeRS和sarA协同作用以抑制细胞外蛋白酶的产生，否则细胞外蛋白酶将限制有助于生物膜形成的关键蛋白质的积累，其中saeRS的组成型激活限制蛋白酶产生，甚至在sarA突变体中，达到可以与形成生物膜的能力增强相关的程度。虽然目前还不清楚这些作用是直接还是间接介导的，但使用sspA：：lux报告基因进行的研究表明，它们是在转录水平介导的。
Mutation of the staphylococcal accessory regulator (sarA) limits biofilm formation in diverse strains of Staphylococcus aureus, but there are exceptions. One of these is the commonly studied strain Newman. This strain has two defects of potential relevance, the first being mutations that preclude anchoring of the fibronectin-binding proteins FnbA and FnbB to the cell wall, and the second being a point mutation in saeS that results in constitutive activation of the saePQRS regulatory system. We repaired these defects to determine whether either plays a role in biofilm formation and, if so, whether this could account for the reduced impact of sarA in Newman. Restoration of surface-anchored FnbA enhanced biofilm formation, but mutation of sarA in this fnbA-positive strain increased rather than decreased biofilm formation. Mutation of sarA in an saeS-repaired derivative of Newman (P18L) or a Newman saeRS mutant (ΔsaeRS) resulted in a biofilm-deficient phenotype like that observed in clinical isolates, even in the absence of surface-anchored FnbA. These phenotypes were correlated with increased production of extracellular proteases and decreased accumulation of FnbA and/or Spa in the P18L and ΔsaeRS sarA mutants by comparison to the Newman sarA mutant. The reduced accumulation of Spa was reversed by mutation of the gene encoding aureolysin, while the reduced accumulation of FnbA was reversed by mutation of the sspABC operon. These results demonstrate that saeRS and sarA act synergistically to repress the production of extracellular proteases that would otherwise limit accumulation of critical proteins that contribute to biofilm formation, with constitutive activation of saeRS limiting protease production, even in a sarA mutant, to a degree that can be correlated with increased enhanced capacity to form a biofilm. Although it remains unclear whether these effects are mediated directly or indirectly, studies done with an sspA::lux reporter suggest they are mediated at a transcriptional level.
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影响因子：
3.1
作者：
Beenken, KE;Blevins, JS;Smeltzer, MS
通讯作者：
Smeltzer, MS
影响因子：
3.1
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影响因子：
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作者：
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影响因子：
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影响因子：
3.4
作者：
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通讯作者：
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