Identification and characterization of sigma, a novel component of the Staphylococcus aureus stress and virulence responses.
Identification and characterization of sigma, a novel component of the Staphylococcus aureus stress and virulence responses.
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DOI：
10.1371/journal.pone.0003844
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Potempa J
中科院分区：
文献类型：
--
作者：
Shaw LN;Lindholm C;Prajsnar TK;Miller HK;Brown MC;Golonka E;Stewart GC;Tarkowski A;Potempa J
S.金黄色葡萄球菌是一种非常成功的病原体，据推测是人类疾病的最常见原因。S.金黄色葡萄球菌响应于生长期间遇到的环境而受到多因子调节。这种适应性被认为是发病机制的核心，是基因调控中采用的多种调控机制的结果。在这项工作中，我们描述了一个小说S的存在。金黄色葡萄球菌调节因子，一种尚未表征的ECF-sigma因子（σS），似乎是该生物体的应激和致病反应的重要组分。使用生物化学方法，我们已经证明σS能够与核心RNAP结合，并从其自身的编码区启动转录。使用突变株，我们确定了σS对S.金黄色葡萄球菌在饥饿、延长暴露于升高的生长温度和Triton X-100诱导的裂解期间的存活。共培养研究表明，σS突变体的竞争力明显低于其亲本菌株，仅在长时间生长（7天）或存在应激化合物的情况下才会加剧。有趣的是，转录分析确定在标准条件下，S。金黄色葡萄球菌SH 1000不启动sigS的表达。每小时进行一次，持续72小时的测定揭示了在典型背景范围内的表达。潜在的反sigma因子，编码的sigS下游的分析，揭示了它没有明显的作用，在sigS表达的上调。使用脓毒性关节炎的小鼠模型，sigS突变体感染的动物体重减轻显著更少，脓毒性关节炎的发生水平显著更低，并且存活率增加。安装的免疫反应的研究表明，sigS-突变体感染的动物具有显著较低的IL-6水平，表明只有弱的免疫反应。最后，S.缺乏sigS的金黄色葡萄球菌更不能够进行全身传播，如通过感染动物的肾脏中的细菌负荷所确定的。这些结果表明σS是S中的一个重要分量。金黄色的健身，并在其适应压力。此外，它似乎在其致病性中起着重要作用，并可能代表了S。aureus调控网络。
S. aureus is a highly successful pathogen that is speculated to be the most common cause of human disease. The progression of disease in S. aureus is subject to multi-factorial regulation, in response to the environments encountered during growth. This adaptive nature is thought to be central to pathogenesis, and is the result of multiple regulatory mechanisms employed in gene regulation. In this work we describe the existence of a novel S. aureus regulator, an as yet uncharacterized ECF-sigma factor (σS), that appears to be an important component of the stress and pathogenic responses of this organism. Using biochemical approaches we have shown that σS is able to associates with core-RNAP, and initiate transcription from its own coding region. Using a mutant strain we determined that σS is important for S. aureus survival during starvation, extended exposure to elevated growth temperatures, and Triton X-100 induced lysis. Coculture studies reveal that a σS mutant is significantly outcompeted by its parental strain, which is only exacerbated during prolonged growth (7 days), or in the presence of stressor compounds. Interestingly, transcriptional analysis determined that under standard conditions, S. aureus SH1000 does not initiate expression of sigS. Assays performed hourly for 72h revealed expression in typically background ranges. Analysis of a potential anti-sigma factor, encoded downstream of sigS, revealed it to have no obvious role in the upregulation of sigS expression. Using a murine model of septic arthritis, sigS-mutant infected animals lost significantly less weight, developed septic arthritis at significantly lower levels, and had increased survival rates. Studies of mounted immune responses reveal that sigS-mutant infected animals had significantly lower levels of IL-6, indicating only a weak immunological response. Finally, strains of S. aureus lacking sigS were far less able to undergo systemic dissemination, as determined by bacterial loads in the kidneys of infected animals. These results establish that σS is an important component in S. aureus fitness, and in its adaptation to stress. Additionally it appears to have a significant role in its pathogenic nature, and likely represents a key component in the S. aureus regulatory network.
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DOI：
10.1073/pnas.0611567104
发表时间：
2007-03-06
影响因子：
11.1
作者：
Cezairliyan, Brent O.;Sauer, Robert T.
通讯作者：
Sauer, Robert T.
影响因子：
5.6
作者：
Bae, JB;Park, JH;Roe, JH
通讯作者：
Roe, JH
DOI：
10.1006/bbrc.1995.1382
发表时间：
1995-03-17
影响因子：
3.1
作者：
DEORA, R;MISRA, TK
通讯作者：
MISRA, TK
影响因子：
3.2
作者：
Doherty, N;Holden, MTG;Winzer, K
通讯作者：
Winzer, K
影响因子：
2.8
作者：
GIRAUDO, AT;RASPANTI, CG;NAGEL, R
通讯作者：
NAGEL, R