Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2011;6(12):e28781. doi: 10.1371/journal.pone.0028781. Epub 2011 Dec 12.
The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus.
酚可溶性调节素 PSM-mec 是唯一已知的葡萄球菌毒素，其编码在一个可移动的抗生素耐药决定因子上，即编码耐甲氧西林的葡萄球菌盒式染色体 (SCC) 元件 mec。在这里，我们发现 psm-mec 基因经常存在于 SCCmec 类型 II、III 和 VIII 的耐甲氧西林金黄色葡萄球菌 (MRSA) 菌株中，并且是 A 类 mec 基因复合物的保守部分。在所有 3 种 psm-mec 阳性 SCCmec 类型的 agr 突变体中控制 AgrA 与 RNAIII 的表达表明，高度可变的 psm-mec 表达受 AgrA 以 RNAIII 独立的方式控制。此外，与相应的野生型菌株相比，psm-mec 基因同型缺失突变体在皮肤感染的小鼠模型中仅显示 PSMα 肽产生的微小变化，并且毒力未改变（或如先前所述，减弱）。这表明最近报道的 psm-mec 基因座对 MRSA 毒力的调节影响与 PSM-mec 肽相反，并且可能由调节 RNA 介导，在原始菌株背景中分析时影响较小。我们的研究为 PSM-mec 肽和 psm-mec 基因座的分布、调节和在毒力中的作用提供了新的见解。
