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Methicillin-resistant\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n                    (MRSA) strains are major pathogens of hospital-acquired and community-acquired infections and are most often treated with glycopeptides (vancomycin and teicoplanin) because of their resistance to most penicillins and a limited arsenal of clinically proven alternatives. In this study, we examined PrsA, a lipid-anchored protein of the parvulin PPIase family (peptidyl-prolyl\n                    <jats:italic>cis\/trans<\/jats:italic>\n                    isomerase) found ubiquitously in all Gram-positive species, in which it assists posttranslocational folding at the outer surface of the cytoplasmic membrane. We show by both genetic and biochemical assays that\n                    <jats:italic>prsA<\/jats:italic>\n                    is directly regulated by the VraRS two-component sentinel system of cell wall stress. Disruption of\n                    <jats:italic>prsA<\/jats:italic>\n                    is tolerated by\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n                    , and its loss results in no detectable overt macroscopic changes in cell wall architecture or growth rate under nonstressed growth conditions. Disruption of\n                    <jats:italic>prsA<\/jats:italic>\n                    leads, however, to notable alterations in the sensitivity to glycopeptides and dramatically decreases the resistance of COL (MRSA) to oxacillin. Quantitative transcriptional analysis reveals that\n                    <jats:italic>prsA<\/jats:italic>\n                    and\n                    <jats:italic>vraR<\/jats:italic>\n                    are coordinately upregulated in a panel of stable laboratory and clinical glycopeptide-intermediate\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n                    (GISA) strains compared to their susceptible parents. Collectively, our results point to a role for\n                    <jats:italic>prsA<\/jats:italic>\n                    as a facultative facilitator of protein secretion or extracellular folding and provide a framework for understanding why\n                    <jats:italic>prsA<\/jats:italic>\n                    is a key element of the VraRS-mediated cell wall stress response.\n                  <\/jats:p>","DOI":"10.1128\/aac.06264-11","type":"journal-article","created":{"date-parts":[[2012,4,24]],"date-time":"2012-04-24T01:01:18Z","timestamp":1335229278000},"page":"3629-3640","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":63,"title":["The Posttranslocational Chaperone Lipoprotein PrsA Is Involved in both Glycopeptide and Oxacillin Resistance in Staphylococcus aureus"],"prefix":"10.1128","volume":"56","author":[{"given":"Ambre","family":"Jousselin","sequence":"first","affiliation":[{"name":"Service of Infectious Diseases, University Hospital and Medical School of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Renzoni","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University Hospital and Medical School of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego O.","family":"Andrey","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University Hospital and Medical School of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Monod","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University Hospital and Medical School of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Lew","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University Hospital and Medical School of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University Hospital and Medical School of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00280-09"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07665.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00146-10"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01000-07"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404728101"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710010200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi900478b"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06143-11"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.13.4085-4099.2004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.3.1028-1036.2003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2006.00384.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(97)00116-X"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-291"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02178-10"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-11-16"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr070521m"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(66)90182-6"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021323"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.19.5723-5725.1995"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/346207"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00720-10"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00720-10"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.091208.073214"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00356-06"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1472-6807-9-17","article-title":"Solution structure of the parvulin-type PPIase domain of Staphylococcus aureus PrsA\u2014implications for the catalytic mechanism of parvulins","volume":"9","author":"Heikkinen O","year":"2009","unstructured":"HeikkinenO . 2009. 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