A Membrane-Bound Transcription Factor is Proteolytically Regulated by the AAA+ Protease FtsH in Staphylococcus aureus
A Membrane-Bound Transcription Factor is Proteolytically Regulated by the AAA+ Protease FtsH in Staphylococcus aureus
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DOI：
10.1128/jb.00019-20
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发表时间：
2020-02
影响因子：
3.2
通讯作者：
Won-sik Yeo;Chiamara Anokwute;P. Marcadis;Marcus Levitan;M. Ahmed;Y. Bae;K. Kim;T. Kostrominova;Qian Liu;T. Bae
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文献类型：
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作者：
Won-sik Yeo;Chiamara Anokwute;P. Marcadis;Marcus Levitan;M. Ahmed;Y. Bae;K. Kim;T. Kostrominova;Qian Liu;T. Bae
金黄色葡萄球菌是引起人类多种疾病的重要致病菌。在细菌中，转录通常由位于细胞质中的转录因子调节。在这项研究中，我们报告了一种在金黄色葡萄球菌中发现的非典型转录因子。与大多数其他转录因子不同，新发现的转录因子位于细胞质膜上，其活性受膜结合的AAA+蛋白酶FtsH的蛋白水解控制。新发现的MTF，被命名为MbtS，有可能调节200多个基因的转录。本研究提供了一种蛋白酶影响细菌转录的分子机制，并说明了细菌转录调控的多样性。在细菌中，染色体DNA驻留在细胞质中，大多数转录因子也存在于细胞质中。然而，一些转录因子，称为膜结合转录因子（MTFs），驻留在细胞质膜上。在这里，我们报道了在革兰氏阳性病原体金黄色葡萄球菌中发现的一种新的MTF及其受蛋白酶FtsH的调控。该MTF被命名为MbtS（金黄色葡萄球菌的膜结合转录因子），由SAUSA300_2640编码，预计具有一个n端DNA结合域和三个跨膜螺旋。用含FtsH的膜泡或纯化后的FtsH降解MbtS蛋白。MbtS与启动子区域的反向重复序列结合，DNA结合对其转录至关重要。ftsH缺失突变体和ftsH mbtS双突变体的转录比较表明，mbtS可以改变200多个基因的转录。虽然在液体培养基中培养的野生型（WT）细胞中未检测到MbtS蛋白，但在琼脂平板上的一些分离菌落中检测到该蛋白。在小鼠皮肤感染模型中，mbtS的破坏增加了病变的大小。基于这些结果，我们认为MbtS是一种新的金黄色葡萄球菌MTF，其活性受FtsH蛋白水解调节。金黄色葡萄球菌是引起人类多种疾病的重要致病菌。在细菌中，转录通常由位于细胞质中的转录因子调节。在这项研究中，我们报告了一种在金黄色葡萄球菌中发现的非典型转录因子。与大多数其他转录因子不同，新发现的转录因子位于细胞质膜上，其活性受膜结合的AAA+蛋白酶FtsH的蛋白水解控制。新发现的MTF，被命名为MbtS，有可能调节200多个基因的转录。本研究提供了一种蛋白酶影响细菌转录的分子机制，并说明了细菌转录调控的多样性。
Staphylococcus aureus is an important pathogenic bacterium causing various diseases in humans. In the bacterium, transcription is typically regulated by the transcription factors located in the cytoplasm. In this study, we report an atypical transcription factor identified in S. aureus. Unlike most other transcription factors, the newly identified transcription factor is located in the cytoplasmic membrane, and its activity is proteolytically controlled by the membrane-bound AAA+ protease FtsH. The newly identified MTF, named MbtS, has the potential to regulate the transcription of over 200 genes. This study provides a molecular mechanism by which a protease affects bacterial transcription and illustrates the diversity of the bacterial transcriptional regulation. ABSTRACT In bacteria, chromosomal DNA resides in the cytoplasm, and most transcription factors are also found in the cytoplasm. However, some transcription factors, called membrane-bound transcription factors (MTFs), reside in the cytoplasmic membrane. Here, we report the identification of a new MTF in the Gram-positive pathogen Staphylococcus aureus and its regulation by the protease FtsH. The MTF, named MbtS (membrane-bound transcription factor of Staphylococcus aureus), is encoded by SAUSA300_2640 and predicted to have an N-terminal DNA binding domain and three transmembrane helices. The MbtS protein was degraded by membrane vesicles containing FtsH or by the purified FtsH. MbtS bound to an inverted repeat sequence in its promoter region, and the DNA binding was essential for its transcription. Transcriptional comparison between the ftsH deletion mutant and the ftsH mbtS double mutant showed that MbtS could alter the transcription of over 200 genes. Although the MbtS protein was not detected in wild-type (WT) cells grown in a liquid medium, the protein was detected in some isolated colonies on an agar plate. In a murine model of a skin infection, the disruption of mbtS increased the lesion size. Based on these results, we concluded that MbtS is a new S. aureus MTF whose activity is proteolytically regulated by FtsH. IMPORTANCE Staphylococcus aureus is an important pathogenic bacterium causing various diseases in humans. In the bacterium, transcription is typically regulated by the transcription factors located in the cytoplasm. In this study, we report an atypical transcription factor identified in S. aureus. Unlike most other transcription factors, the newly identified transcription factor is located in the cytoplasmic membrane, and its activity is proteolytically controlled by the membrane-bound AAA+ protease FtsH. The newly identified MTF, named MbtS, has the potential to regulate the transcription of over 200 genes. This study provides a molecular mechanism by which a protease affects bacterial transcription and illustrates the diversity of the bacterial transcriptional regulation.