{"entity": "researcher", "timestamp": "2026-09-23T23:13:56.623Z", "family": "Hughes", "given": "Diarmaid", "initials": "D", "orcid": "0000-0002-7456-9182", "affiliations": ["Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Uppsala SE-75123, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3977477b57784a1bb16dece0d61c5896.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3977477b57784a1bb16dece0d61c5896"}}, "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"}, {"entity": "publication", "iuid": "0ef688fcd9e44aaab29d7d0342978543", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0ef688fcd9e44aaab29d7d0342978543.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0ef688fcd9e44aaab29d7d0342978543"}}, "title": "Evolution of Bacterial Interspecies Hybrids with Enlarged Chromosomes.", "authors": [{"family": "Bartke", "given": "Katrin", "initials": "K", "orcid": "0000-0003-3033-8830", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2537458db85e4d9dbe5115c5c672702a.json"}}, {"family": "Huseby", "given": "Douglas L", "initials": "DL", "orcid": "0000-0001-9974-578X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a46951ada9ef48b081abd9a244d45cc1.json"}}, {"family": "Brandis", "given": "Gerrit", "initials": "G", "orcid": "0000-0001-8457-7699", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4c06132153a54ae8bb2b1ca969e7597e.json"}}, {"family": "Hughes", "given": "Diarmaid", "initials": "D", "orcid": "0000-0002-7456-9182", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3977477b57784a1bb16dece0d61c5896.json"}}], "type": "journal article", "published": "2022-10-07", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "14", "issue": "10", "issn-l": "1759-6653"}, "abstract": "Conjugation driven by a chromosomally integrated F-plasmid (high frequency of recombination strain) can create bacteria with hybrid chromosomes. Previous studies of interspecies hybrids have focused on hybrids in which a region of donor chromosome replaces an orthologous region of recipient chromosome leaving chromosome size unchanged. Very little is known about hybrids with enlarged chromosomes, the mechanisms of their creation, or their subsequent trajectories of adaptative evolution. We addressed this by selecting 11 interspecies hybrids between Escherichia coli and Salmonella Typhimurium in which genome size was enlarged. In three cases, this occurred by the creation of an F'-plasmid while in the remaining eight, it was due to recombination of donor DNA into the recipient chromosome. Chromosome length increased by up to 33% and was associated in most cases with reduced growth fitness. Two hybrids, in which chromosome length was increased by the addition of 0.97 and 1.3 Mb, respectively, were evolved to study genetic pathways of fitness cost amelioration. In each case, relative fitness rapidly approached one and this was associated with large deletions involving recombination between repetitive DNA sequences. The locations of these repetitive sequences played a major role in determining the architecture of the evolved genotypes. Notably, in ten out of ten independent evolution experiments, deletions removed DNA of both species, creating high-fitness strains with hybrid chromosomes. In conclusion, we found that enlargement of a bacterial chromosome by acquisition of diverged orthologous DNA is followed by a period of rapid evolutionary adjustment frequently creating irreversibly hybrid chromosomes.", "doi": "10.1093/gbe/evac135", "pmid": "36073531", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9551528"}, {"db": "pii", "key": "6693946"}], "notes": [], "created": "2026-09-23T13:16:32.842Z", "modified": "2026-09-23T13:16:32.970Z"}]}