{"entity": "researcher", "timestamp": "2026-07-22T16:39:15.911Z", "family": "Normark", "given": "Staffan", "initials": "S", "orcid": "0000-0001-7917-3921", "affiliations": ["Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden; staffan.normark@ki.se birgitta.henriques@ki.se.", "Lee Kong Chian School of Medicine and Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 639798, Singapore."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/72caf78541474b5bbbc2049facb70954.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/72caf78541474b5bbbc2049facb70954"}}, "publications": [{"entity": "publication", "iuid": "f5c19c72ccc44fe99833a66862c769d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5c19c72ccc44fe99833a66862c769d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5c19c72ccc44fe99833a66862c769d5"}}, "title": "THCz: Small molecules with antimicrobial activity that block cell wall lipid intermediates.", "authors": [{"family": "Reithuber", "given": "Elisabeth", "initials": "E"}, {"family": "Wixe", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Ludwig", "given": "Kevin C", "initials": "KC"}, {"family": "M\u00fcller", "given": "Anna", "initials": "A"}, {"family": "Uvell", "given": "Hanna", "initials": "H"}, {"family": "Grein", "given": "Fabian", "initials": "F"}, {"family": "Lindgren", "given": "Anders E G", "initials": "AEG"}, {"family": "Muschiol", "given": "Sandra", "initials": "S"}, {"family": "Nannapaneni", "given": "Priyanka", "initials": "P"}, {"family": "Eriksson", "given": "Anna", "initials": "A"}, {"family": "Schneider", "given": "Tanja", "initials": "T"}, {"family": "Normark", "given": "Staffan", "initials": "S", "orcid": "0000-0001-7917-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/72caf78541474b5bbbc2049facb70954.json"}}, {"family": "Henriques-Normark", "given": "Birgitta", "initials": "B"}, {"family": "Almqvist", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-0504-4446", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f8d848fccce44da9bcd4e79f7eae64c.json"}}, {"family": "Mellroth", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2021-11-23", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "issn-l": "0027-8424", "volume": "118", "issue": "47", "pages": null}, "abstract": "Emerging antibiotic resistance demands identification of novel antibacterial compound classes. A bacterial whole-cell screen based on pneumococcal autolysin-mediated lysis induction was developed to identify potential bacterial cell wall synthesis inhibitors. A hit class comprising a 1-amino substituted tetrahydrocarbazole (THCz) scaffold, containing two essential amine groups, displayed bactericidal activity against a broad range of gram-positive and selected gram-negative pathogens in the low micromolar range. Mode of action studies revealed that THCz inhibit cell envelope synthesis by targeting undecaprenyl pyrophosphate-containing lipid intermediates and thus simultaneously inhibit peptidoglycan, teichoic acid, and polysaccharide capsule biosynthesis. Resistance did not readily develop in vitro, and the ease of synthesizing and modifying these small molecules, as compared to natural lipid II-binding antibiotics, makes THCz promising scaffolds for development of cell wall-targeting antimicrobials.", "doi": "10.1073/pnas.2108244118", "pmid": "34785593", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "2108244118"}], "notes": [], "created": "2021-11-24T10:29:51.162Z", "modified": "2025-10-17T13:04:27.992Z"}, {"entity": "publication", "iuid": "2d03d3eccf51447f8598cb76587b9f98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d03d3eccf51447f8598cb76587b9f98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d03d3eccf51447f8598cb76587b9f98"}}, "title": "Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways.", "authors": [{"family": "Sender", "given": "Vicky", "initials": "V", "orcid": "0000-0003-2174-946X", "researcher": {"href": "https://publications.scilifelab.se/researcher/806e259d26014318a915ebe132bafb5d.json"}}, {"family": "Hentrich", "given": "Karina", "initials": "K", "orcid": "0000-0001-6660-7233", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dfc3f0078864e68baf26086869ab2d5.json"}}, {"family": "Pathak", "given": "Anuj", "initials": "A"}, {"family": "Tan Qian Ler", "given": "Alicia", "initials": "A", "orcid": "0000-0001-9298-4008", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba872b0c12754f6bb57015ede1d10755.json"}}, {"family": "Embaie", "given": "Bethel Tesfai", "initials": "BT", "orcid": "0000-0002-7081-5032", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc274efbd34147e3972c85858d252a37.json"}}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Bergstrand", "given": "Jan", "initials": "J"}, {"family": "Nakamoto", "given": "Rei", "initials": "R", "orcid": "0000-0001-7807-6548", "researcher": {"href": "https://publications.scilifelab.se/researcher/07fdc7bfbb58498d986542fd1ea2cdce.json"}}, {"family": "Sham", "given": "Lok-To", "initials": "L"}, {"family": "Widengren", "given": "Jerker", "initials": "J"}, {"family": "Normark", "given": "Staffan", "initials": "S", "orcid": "0000-0001-7917-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/72caf78541474b5bbbc2049facb70954.json"}}, {"family": "Henriques-Normark", "given": "Birgitta", "initials": "B"}], "type": "journal article", "published": "2020-12-08", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "issn-l": "0027-8424", "volume": "117", "issue": "49", "pages": "31386-31397"}, "abstract": "Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.", "doi": "10.1073/pnas.2012265117", "pmid": "33229573", "labels": {"Chemical Proteomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "2012265117"}, {"db": "pmc", "key": "PMC7733805"}], "notes": [], "created": "2020-11-30T11:01:05.695Z", "modified": "2024-01-18T23:34:47.832Z"}]}