{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:49:53Z","timestamp":1792705793397,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01AI100291"],"award-info":[{"award-number":["2R01AI100291"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>\u03b2-lactam antibiotics are excellent drugs for treatment of staphylococcal infections, due to their superior efficacy and safety compared to other drugs. Effectiveness of \u03b2-lactams is severely compromised due to resistance, which is widespread among clinical strains of Staphylococcus aureus. \u03b2-lactams inhibit bacterial cells by binding to penicillin binding proteins (PBPs), which perform the penultimate steps of bacterial cell wall synthesis. Among PBPs of S. aureus, PBP2a has received the most attention for the past several decades due to its preeminent role in conferring both high-level and broad-spectrum resistance to the entire class of \u03b2-lactam drugs. Studies on PBP2a have thus unraveled incredible details of its mechanism of action. We have recently identified that an uncanonical, low molecular weight PBP of S. aureus, PBP4, can also provide high-level and broad-spectrum resistance to the entire class of \u03b2-lactam drugs at a level similar to that of PBP2a. The role of PBP4 has typically been considered not so important for \u03b2-lactam resistance of S. aureus, and as a result its mode of action remains largely unknown. In this article, we review our current knowledge of PBP4 mediating \u03b2-lactam resistance in S. aureus.<\/jats:p>","DOI":"10.3390\/microorganisms6030057","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T10:56:28Z","timestamp":1529664988000},"page":"57","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["PBP4: A New Perspective on Staphylococcus aureus \u03b2-Lactam Resistance"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3660-1786","authenticated-orcid":false,"given":"Thaina M.","family":"Da Costa","sequence":"first","affiliation":[{"name":"Division of HIV\/AIDS, Infectious Diseases and Global Health, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Bldg. 30, San Francisco, CA 94110, USA"},{"name":"Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina R.","family":"De Oliveira","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS, Infectious Diseases and Global Health, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Bldg. 30, San Francisco, CA 94110, USA"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade de Bras\u00edlia, Campus Universit\u00e1rio Darcy Ribeiro, Bras\u00edlia, CEP 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry F.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS, Infectious Diseases and Global Health, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Bldg. 30, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Som S.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS, Infectious Diseases and Global Health, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Bldg. 30, San Francisco, CA 94110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrmicro2200","article-title":"Waves of resistance: Staphylococcus aureus in the antibiotic era","volume":"7","author":"Chambers","year":"2009","journal-title":"Nat. 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