{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:50:20Z","timestamp":1778028620055,"version":"3.51.4"},"reference-count":28,"publisher":"Proceedings of the National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,9,11]]},"abstract":"<jats:p>\n                    The blanket resistance of methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    to all \u03b2-lactam antibiotics\u2014which had such a devastating impact on chemotherapy of staphylococcal infections\u2014is related to the properties of the key component of this resistance mechanism: the \u201cacquired\u201d penicillin-binding protein (PBP)-2A, which has unusual low affinity for all \u03b2-lactam antibiotics. Until now, the accepted model of resistance implied that in the presence of \u03b2-lactam antibiotics in the surrounding medium, PBP2A must take over the biosynthesis of staphylococcal cell wall from the four native staphylococcal PBPs because the latter become rapidly acylated and inactivated at even low concentrations of the antibiotic. However, recent observations indicate that this model requires revision. Inactivation of the transglycosylase domain, but not the transpeptidase domain, of PBP2 of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    prevents expression of \u03b2-lactam resistance, despite the presence of the low-affinity PBP2A. The observations suggest that cell-wall synthesis in the presence of \u03b2-lactam antibiotics requires the cooperative functioning of the transglycosylase domain of the native staphylococcal PBP2 and the transpeptidase domain of the PBP2A, a protein imported by\n                    <jats:italic>S. aureus<\/jats:italic>\n                    from an extra species source.\n                  <\/jats:p>","DOI":"10.1073\/pnas.191260798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"10886-10891","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":311,"title":["An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci"],"prefix":"10.1073","volume":"98","author":[{"given":"Mariana G.","family":"Pinho","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, The Rockefeller University, New York, NY 10021; and Molecular Genetics Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780 Oeiras, Portugal"}]},{"given":"Herm\u00ednia","family":"de Lencastre","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, The Rockefeller University, New York, NY 10021; and Molecular Genetics Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780 Oeiras, Portugal"}]},{"given":"Alexander","family":"Tomasz","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, The Rockefeller University, New York, NY 10021; and Molecular Genetics Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780 Oeiras, Portugal"}]}],"member":"341","published-online":{"date-parts":[[2001,8,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.165.2.373-378.1986"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.135.2.460-465.1978"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80373-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1989.tb15104.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.4.1079-1093.1998"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.158.2.513-516.1984"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(85)80036-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.1997.3.409"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/161.6.1170"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1994.tb06754.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.4.1074-1079.2000"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.8.2417-2424.2001"},{"key":"e_1_3_3_13_2","volume-title":"Current Protocols In Molecular Biology","author":"Ausubel F M","year":"1996","unstructured":"F M Ausubel, R Brent, R E Kingston, D D Moore, J G Seidman, J A Smith, K Struhl Current Protocols In Molecular Biology (Wiley, New York, 1996)."},{"key":"e_1_3_3_14_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"1989","unstructured":"J Sambrook, I Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. 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