{"entity": "researcher", "timestamp": "2026-09-23T23:53:37.490Z", "family": "Olanders", "given": "Gustav", "initials": "G", "orcid": "0000-0003-4713-8368", "affiliations": ["Department of Medicinal Chemistry, BMC, Uppsala University, Uppsala SE-75123, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/67abdf5c2573420a89754f75647c04c9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/67abdf5c2573420a89754f75647c04c9"}}, "publications": [{"entity": "publication", "iuid": "be2ceb3b1c964e8f8848075df52aa2eb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/be2ceb3b1c964e8f8848075df52aa2eb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/be2ceb3b1c964e8f8848075df52aa2eb"}}, "title": "Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria.", "authors": [{"family": "Huseby", "given": "Douglas L", "initials": "DL", "orcid": "0000-0001-9974-578X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a46951ada9ef48b081abd9a244d45cc1.json"}}, {"family": "Cao", "given": "Sha", "initials": "S"}, {"family": "Zamaratski", "given": "Edouard", "initials": "E", "orcid": "0009-0003-2707-3648", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fa8570c2f0748b4b7258afa6da4702e.json"}}, {"family": "Sooriyaarachchi", "given": "Sanjeewani", "initials": "S"}, {"family": "Ahmad", "given": "Shabbir", "initials": "S", "orcid": "0000-0003-2374-1197", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9a9fa8ea9eb43fa9642ff3da5618267.json"}}, {"family": "Bergfors", "given": "Terese", "initials": "T", "orcid": "0000-0002-6463-9116", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e78b0675662e47bab61d190df5cb2203.json"}}, {"family": "Krasnova", "given": "Laura", "initials": "L"}, {"family": "Pelss", "given": "Juris", "initials": "J"}, {"family": "Ikaunieks", "given": "Martins", "initials": "M"}, {"family": "Loza", "given": "Einars", "initials": "E"}, {"family": "Katkevics", "given": "Martins", "initials": "M", "orcid": "0000-0003-1547-0075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac9168c241174ebfad578a075c78ae4a.json"}}, {"family": "Bobileva", "given": "Olga", "initials": "O", "orcid": "0000-0001-9600-1603", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22e7bc2a9a0b47d19241789339a361bf.json"}}, {"family": "Cirule", "given": "Helena", "initials": "H"}, {"family": "Gukalova", "given": "Baiba", "initials": "B", "orcid": "0000-0002-7057-4726", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b5941a1c14d74cfe92b33c496e4ce5bc.json"}}, {"family": "Grinberga", "given": "Solveiga", "initials": "S"}, {"family": "Backlund", "given": "Maria", "initials": "M", "orcid": "0000-0002-6253-816X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3cbe928d448a4669908f38d58bbe5606.json"}}, {"family": "Simoff", "given": "Ivailo", "initials": "I"}, {"family": "Leber", "given": "Anna T", "initials": "AT"}, {"family": "Berruga-Fern\u00e1ndez", "given": "Tal\u00eda", "initials": "T"}, {"family": "Antonov", "given": "Dmitry", "initials": "D"}, {"family": "Konda", "given": "Vivekananda R", "initials": "VR"}, {"family": "Lindstr\u00f6m", "given": "Stefan", "initials": "S", "orcid": "0009-0009-7396-9529", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/63b366b7f46948b8ba5648412eab63a1.json"}}, {"family": "Olanders", "given": "Gustav", "initials": "G", "orcid": "0000-0003-4713-8368", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/67abdf5c2573420a89754f75647c04c9.json"}}, {"family": "Brandt", "given": "Peter", "initials": "P"}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/327feae3833d425c9d5936f48627390c.json"}}, {"family": "Vingsbo Lundberg", "given": "Carina", "initials": "C", "orcid": "0000-0003-3408-3353", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eaa8939eb68b4d4a818ce784e6c7aaa0.json"}}, {"family": "Liepinsh", "given": "Edgars", "initials": "E", "orcid": "0000-0003-2213-8337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3e6a02475a5a423bbc75a9b3de350e2b.json"}}, {"family": "Suna", "given": "Edgars", "initials": "E"}, {"family": "Jones", "given": "T Alwyn", "initials": "TA"}, {"family": "Mowbray", "given": "Sherry L", "initials": "SL", "orcid": "0000-0002-0732-6367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/93f59b3d476e43f1bdf90e120e92e165.json"}}, {"family": "Hughes", "given": "Diarmaid", "initials": "D", "orcid": "0000-0002-7456-9182", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3977477b57784a1bb16dece0d61c5896.json"}}, {"family": "Karl\u00e9n", "given": "Anders", "initials": "A", "orcid": "0000-0001-9512-6981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/032040a93855408fb5955bb3e8893431.json"}}], "type": "journal article", "published": "2024-04-09", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "121", "issue": "15", "pages": "e2317274121", "issn-l": "0027-8424"}, "abstract": "Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-\u03b2-lactamase, metallo-\u03b2-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance.", "doi": "10.1073/pnas.2317274121", "pmid": "38579010", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11009625"}], "notes": [], "created": "2026-09-23T10:10:26.224Z", "modified": "2026-09-23T10:48:44.118Z"}]}