Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence.
Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCCmec regulate Staphylococcus aureus virulence.
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DOI：
10.1371/journal.ppat.1001267
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发表时间：
2011-02-03
期刊：
影响因子：
6.7
通讯作者：
Sekimizu K
中科院分区：
文献类型：
--
作者：
Kaito C;Saito Y;Nagano G;Ikuo M;Omae Y;Hanada Y;Han X;Kuwahara-Arai K;Hishinuma T;Baba T;Ito T;Hiramatsu K;Sekimizu K
医院相关耐甲氧西林金黄色葡萄球菌(HA-MRSA)SCCmec元件mecI基因下游的F区含有两个双向重叠的开放阅读框架(ORF)，即Fudoh ORF和PSM-mec ORF。PSM-mec ORF编码一种细胞溶素，苯酚可溶性调制素(PSM)-mec。在小鼠全身感染模型中，将F区转化为甲氧西林敏感的金黄色葡萄球菌(MSSA)纽曼株，或缺乏F区的社区获得的MRSA(CA-MRSA)MW2(USA400)和FRP3757(USA300)株，可降低它们的毒力。在这些菌株中引入F区可抑制菌落扩散活性和PsMα的产生，并促进生物膜的形成。通过对PSM-mec ORF进行突变，我们发现：(I)PSM-mec ORF的转录和翻译产物都抑制了菌落扩散活性并促进了生物膜的形成；(Ii)PSM-mec ORF的转录产物，但不是其翻译产物，降低了PSMα的产量。这些发现表明，PSM-mec转录本作为调节RNA，以及由移动遗传元件SCCmec上的基因编码的PSM-mec蛋白调节金黄色葡萄球菌的毒力。耐甲氧西林金黄色葡萄球菌(MRSA)在医院引起免疫功能低下患者的机会性传染病，这些疾病很难用抗生素治愈。这些MRSA被称为医院相关MRSA(HA-MRSA)。相比之下，其他MRSA菌株，被称为社区获得的MRSA(CA-MRSA)，毒力高，并在以前健康的个人中引起严重感染。CA-MRSA表型毒力强的原因尚不清楚。MRSA通过获得一种名为SCCmec的外来DNA而对抗生素产生抗药性。SCCmec区域包含几个基因，包括mecA基因，它对甲氧西林具有耐药性。我们将注意力集中在HA-MRSA和CA-MRSA SCCmec区的结构差异上。CA-MRSA的SCCmec区缺少抑制HA-MRSA毒力的F区。在这项研究中，我们揭示了编码在F区的溶细胞素基因PSM-mec的转录和翻译产物都抑制了MRSA的毒力。这一发现有助于我们从分子水平上理解CA-MRSA的高毒力，并将有助于制定新的策略来抗击CA-MRSA引起的传染病。
The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) causes opportunistic infectious diseases in immunocompromised patients in hospitals, which are difficult to cure with antibiotics. These MRSA are called hospital-associated MRSA (HA-MRSA). In contrast, other MRSA strains, which are called community-acquired MRSA (CA-MRSA), have high virulence and cause serious infections in previously healthy individuals. Why the CA-MRSA phenotype has high virulence is not well understood. MRSA becomes resistant to antibiotics by acquiring a foreign DNA called SCCmec. The SCCmec region contains several genes, including the mecA gene, which confers resistance against methicillin. We focused our attention on the structural difference of the SCCmec region between HA-MRSA and CA-MRSA. The SCCmec region of CA-MRSA lacks the F region, which suppresses HA-MRSA virulence. In this study, we revealed that both the transcription and translation products of a cytolysin gene, psm-mec, which is encoded in the F region, suppress MRSA virulence. This finding contributes to our understanding of the high virulence of CA-MRSA at the molecular level and will help to establish new strategies to combat infectious diseases due to CA-MRSA.
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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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DOI：
10.1016/s1473-3099(01)00091-3
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2001-10-01
期刊：
The Lancet. Infectious diseases
影响因子：
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作者：
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通讯作者：
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影响因子：
2.2
作者：
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