Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
PLoS Pathog. 2011 Feb 3;7(2):e1001267. doi: 10.1371/journal.ppat.1001267.
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.
医院相关耐甲氧西林金黄色葡萄球菌（HA-MRSA）中 SCCmec 元件 mecI 基因下游的 F 区包含两个双向重叠的开放阅读框（ORF），fudoh ORF 和 psm-mec ORF。psm-mec ORF 编码细胞毒素、酚可溶性调节素（PSM）-mec。将 F 区转化为耐甲氧西林敏感金黄色葡萄球菌（MSSA）菌株 Newman 或缺乏 F 区的社区获得性耐甲氧西林金黄色葡萄球菌（CA-MRSA）菌株 MW2（USA400）和 FRP3757（USA300），会使其在小鼠全身感染模型中的毒力减弱。向这些菌株中引入 F 区抑制了菌落扩散活性和 PSMα 的产生，并促进了生物膜的形成。通过对 psm-mec ORF 产生突变，我们揭示了（i）psm-mec ORF 的转录和翻译产物均抑制了菌落扩散活性并促进了生物膜的形成；和（ii）psm-mec ORF 的转录产物，而不是其翻译产物，降低了 PSMα 的产生。这些发现表明，作为调节 RNA 的 psm-mec 转录本和移动遗传元件 SCCmec 上基因编码的 PSM-mec 蛋白都调节金黄色葡萄球菌的毒力。
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