SpxA1 involved in hydrogen peroxide production, stress tolerance and endocarditis virulence in Streptococcus sanguinis.

SpxA1 involved in hydrogen peroxide production, stress tolerance and endocarditis virulence in Streptococcus sanguinis.
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DOI:
10.1371/journal.pone.0040034
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Xu P
Xu P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen L;Ge X;Wang X;Patel JR;Xu P

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血链球菌是感染性心内膜炎最常见的致病菌之一。SPX蛋白是一组负向或正向控制全局转录启动的全球调控因子。在本研究中,我们对血链球菌SK36中的spxA1基因进行了研究。与野生型相比,spxA1缺失突变体的菌落形态不透明,过氧化氢(H_2O_2)产生减少,对变形链球菌UA159的拮抗活性降低。ΔspxA1突变体还表现出对高温、酸性和氧化应激的耐受性降低。进一步的分析显示,在心内膜炎动物模型中,ΔspxA1还显示出∼竞争力降低5倍。微阵列研究表明,在ΔspxA1突变体中,几个氧化应激基因的表达下调。与野生型相比,ΔspxA1突变体中spxB和NOx的表达显著降低。这些结果表明,spxA1在血链球菌SK36的过氧化氢产生、应激耐受性和心内膜炎毒力中起重要作用。在血链球菌SK36中也发现了第二个spx基因spxA2。SpxA2缺失突变体在正常条件下存在生长缺陷,对高温、酸性和氧化胁迫表现出敏感性。
Streptococcus sanguinis is one of the most common agents of infective endocarditis. Spx proteins are a group of global regulators that negatively or positively control global transcription initiation. In this study, we characterized the spxA1 gene in S. sanguinis SK36. The spxA1 null mutant displayed opaque colony morphology, reduced hydrogen peroxide (H2O2) production, and reduced antagonistic activity against Streptococcus mutans UA159 relative to the wild type strain. The ΔspxA1 mutant also demonstrated decreased tolerance to high temperature, acidic and oxidative stresses. Further analysis revealed that ΔspxA1 also exhibited a ∼5-fold reduction in competitiveness in an animal model of endocarditis. Microarray studies indicated that expression of several oxidative stress genes was downregulated in the ΔspxA1 mutant. The expression of spxB and nox was significantly decreased in the ΔspxA1 mutant compared with the wild type. These results indicate that spxA1 plays a major role in H2O2 production, stress tolerance and endocarditis virulence in S. sanguinis SK36. The second spx gene, spxA2, was also found in S. sanguinis SK36. The spxA2 null mutant was found to be defective for growth under normal conditions and showed sensitivity to high temperature, acidic and oxidative stresses.
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