distribution and regulation of the mobile genetic element-encoded phenol-soluble modulin psm-mec in methicillin-resistant staphylococcus aureus分配和调节移动遗传element-encoded phenol-soluble modulin psm-mec耐甲氧西林金黄色葡萄球菌.pdfVIP

Distribution and Regulation of the Mobile Genetic Element-Encoded Phenol-Soluble Modulin PSM-mec in Methicillin-Resistant Staphylococcus aureus 1 2 1 1 2 Som S. Chatterjee , Liang Chen , Hwang-Soo Joo , Gordon Y. C. Cheung , Barry N. Kreiswirth , Michael Otto1* 1 Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, United States of America, 2 Public Health Research Institute Tuberculosis Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America Abstract 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 PSMa 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 media