{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:24:50Z","timestamp":1787649890488,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"University of Notre Dame","doi-asserted-by":"publisher","award":["P50 AR072000"],"award-info":[{"award-number":["P50 AR072000"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P50 AR072000"],"award-info":[{"award-number":["P50 AR072000"]}],"id":[{"id":"https:\/\/ror.org\/00mkhxb43","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Family Fellowship for Research on Cystic Fibrosis"},{"name":"Bethiaume Institute for Precision Health Graduate Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for new antibacterial agents. Here, we report the identification and evaluation of a novel Gram-positive selective antibacterial: NDM-552. Methods: Antibacterial activity was determined by broth microdilution against a panel of Gram-positive and Gram-negative pathogens. Mechanistic studies included BOCILLIN-FL competition assays, microscale thermophoresis (MST), and antibiotic interaction with oxacillin and moenomycin. Additionally, time\u2013kill analyses, frequency-of-resistance measurements, cytotoxicity assays, plasma stability studies, and a murine wound infection model were performed to characterize NDM-552. Results: NDM-552 exhibits activity against Gram-positive pathogens including S. aureus, Enterococcus faecium, and Staphylococcus epidermidis, with minimum inhibitory concentrations (MICs) of 1\u20132 \u00b5g\/mL. NDM-552 displays no activity against Gram-negative bacteria. NDM-552 displays bacteriostatic activity against MRSA and additive interactions with oxacillin and moenomycin. The frequency of resistance in MRSA is low (2.39 \u00d7 10\u22129). BOCILLIN-FL competition assays and MST binding analysis identify the essential penicillin-binding protein 2 (PBP2) as the potential target of NDM-552. NDM-552 demonstrates acceptable cytotoxicity, favorable plasma stability, and reduces bacterial burden in a murine wound infection model. Conclusions: NDM-552 is a potent Gram-positive selective antibacterial agent that potentially targets PBP2-associated cell wall biosynthesis and exhibits in vivo efficacy against MRSA. Findings establish NDM-552 as a promising scaffold for the development of new antibacterial agents.<\/jats:p>","DOI":"10.3390\/antibiotics15090826","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:04:30Z","timestamp":1787648670000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of a Novel Benzothiophene Inhibitor of Penicillin-Binding Protein 2 with Potent Gram-Positive Activity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9293-1222","authenticated-orcid":false,"given":"Monica A.","family":"Stefaniak","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5603-7345","authenticated-orcid":false,"given":"Vijay Singh","family":"Gondil","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1303-9007","authenticated-orcid":false,"given":"Jingdong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-1127","authenticated-orcid":false,"given":"Allen G.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7249-5688","authenticated-orcid":false,"given":"Ansley M.","family":"Nemeth","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-3351","authenticated-orcid":false,"given":"Roberta J.","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-3775","authenticated-orcid":false,"given":"Mayland","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Dunman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mulani, M.S., Kamble, E.E., Kumkar, S.N., Tawre, M.S., and Pardesi, K.R. 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