{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:20:04Z","timestamp":1787008804008,"version":"build-2736575974"},"reference-count":64,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":136,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007137","name":"Northern Norway Regional Health Authority","doi-asserted-by":"publisher","award":["HNF1570-21"],"award-info":[{"award-number":["HNF1570-21"]}],"id":[{"id":"10.13039\/501100007137","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"publisher","award":["295910"],"award-info":[{"award-number":["295910"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enterococcus faecium is a gut commensal bacterium which is gaining increasing relevance as an opportunistic, nosocomial pathogen. Its high level of intrinsic and acquired antimicrobial resistance is causing a lack of treatment options, particularly for infections with vancomycin-resistant strains, and prioritizes the identification and functional validation of novel druggable targets. Here, we use activity-based protein profiling (ABPP), a chemoproteomics approach using functionalized covalent inhibitors, to detect active serine hydrolases across 11 E. faecium and Enterococcus lactis strains. Serine hydrolases are a big and diverse enzyme family, that includes known drug targets such as penicillin-binding proteins (PBPs), whereas other subfamilies are underexplored. Comparative gel-based ABPP using Bocillin-FL revealed strain- and growth condition-dependent variations in PBP activities. Profiling with the broadly serine hydrolase-reactive fluorescent probe fluorophosphonate-TMR showed a high similarity across E. faecium clade A1 strains, but higher variation across A2 and E. lactis strains. To identify these serine hydrolases, we used a biotinylated probe analog allowing for enrichment and identification via liquid chromatography\u2013mass spectrometry. We identified 11 largely uncharacterized targets (\u03b1,\u03b2-hydrolases, SGNH-hydrolases, phospholipases, and amidases, peptidases) that are druggable and accessible in live vancomycin-resistant E. faecium E745 and may possess vital functions that are to be characterized in future studies.<\/jats:p>","DOI":"10.1093\/femsmc\/xtae015","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:47:03Z","timestamp":1715705223000},"source":"Crossref","is-referenced-by-count":10,"title":["Activity-based protein profiling of serine hydrolases and penicillin-binding proteins in\n                    <i>Enterococcus faecium<\/i>"],"prefix":"10.1093","volume":"5","author":[{"given":"Jeanette S","family":"Grunnv\u00e5g","sequence":"first","affiliation":[{"name":"Research Group for Host-Microbe Interactions, Department of Medical Biology, UiT \u2013 The Arctic University of Norway , Postboks 6050 Langnes, 9037 Troms\u00f8 , Norway"},{"name":"Centre for New Antibacterial Strategies (CANS), UiT \u2013 The Arctic University of Norway , Postboks 6050 Langnes, 9037 Troms\u00f8 , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-0497","authenticated-orcid":false,"given":"Kristin","family":"Hegstad","sequence":"additional","affiliation":[{"name":"Research Group for Host-Microbe Interactions, Department of Medical Biology, UiT \u2013 The Arctic University of Norway , Postboks 6050 Langnes, 9037 Troms\u00f8 , Norway"},{"name":"Centre for New Antibacterial Strategies (CANS), UiT \u2013 The Arctic University of Norway , Postboks 6050 Langnes, 9037 Troms\u00f8 , Norway"},{"name":"Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway , P.O. Box 56, 9038 Troms\u00f8 , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-2264","authenticated-orcid":false,"given":"Christian S","family":"Lentz","sequence":"additional","affiliation":[{"name":"Research Group for Host-Microbe Interactions, Department of Medical Biology, UiT \u2013 The Arctic University of Norway , Postboks 6050 Langnes, 9037 Troms\u00f8 , Norway"},{"name":"Centre for New Antibacterial Strategies (CANS), UiT \u2013 The Arctic University of Norway , Postboks 6050 Langnes, 9037 Troms\u00f8 , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"2024052909263161700_bib1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nchembio.579","article-title":"Click-generated triazole ureas as ultrapotent in vivo\u2013active serine hydrolase 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