{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:53:23Z","timestamp":1790225603547,"version":"4.1.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI118874"],"award-info":[{"award-number":["AI118874"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Methicillin-resistant\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. We present here results that demonstrate differing extents of synergy between TXA707 and a broad range of \u03b2-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each \u03b2-lactam, we determined the binding affinities of the \u03b2-lactam antibiotics for each of the four native penicillin-binding proteins (PBPs) of\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            using a fluorescence anisotropy competition assay. A comparison of the resulting PBP binding affinities with our corresponding synergy results reveals that \u03b2-lactams with a high affinity for PBP2 afford the greatest degree of synergy with TXA707 against MRSA. In addition, we present fluorescence and electron microscopy studies that suggest a potential mechanism underlying the synergy between TXA707 and the \u03b2-lactam antibiotics. In this connection, our microscopy results show a disruption of septum formation in TXA707-treated MRSA cells, with a concomitant mislocalization of the PBPs from midcell to nonproductive peripheral sites. Viewed as a whole, our results indicate that PBP2-targeting \u03b2-lactam antibiotics are optimal synergistic partners with FtsZ-targeting agents for use in combination therapy of MRSA infections.\n          <\/jats:p>","DOI":"10.1128\/aac.00863-17","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:30:28Z","timestamp":1497918628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["\u03b2-Lactam Antibiotics with a High Affinity for PBP2 Act Synergistically with the FtsZ-Targeting Agent TXA707 against Methicillin-Resistant Staphylococcus aureus"],"prefix":"10.1128","volume":"61","author":[{"given":"Edgar","family":"Ferrer-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malvika","family":"Kaul","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit K.","family":"Parhi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, New Jersey, USA"},{"name":"TAXIS Pharmaceuticals, Inc., Monmouth Junction, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond J.","family":"LaVoie","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Pilch","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Antimicrobial resistance: global report on surveillance","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. 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