{"entity": "researcher", "timestamp": "2026-07-22T17:36:48.903Z", "family": "Knopp", "given": "Michael", "initials": "M", "orcid": "0000-0002-8218-3263", "affiliations": ["Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/7e2620cb646745b892428f758597f78e.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/7e2620cb646745b892428f758597f78e"}}, "publications": [{"entity": "publication", "iuid": "7c0db5cdb6844734a45a079ac25ca47b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c0db5cdb6844734a45a079ac25ca47b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c0db5cdb6844734a45a079ac25ca47b"}}, "title": "A novel type of colistin resistance genes selected from random sequence space.", "authors": [{"family": "Knopp", "given": "Michael", "initials": "M", "orcid": "0000-0002-8218-3263", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2620cb646745b892428f758597f78e.json"}}, {"family": "Babina", "given": "Arianne M", "initials": "AM", "orcid": "0000-0002-4635-8396", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbe7f6d7d7a64bc3b829bea72dc1ca63.json"}}, {"family": "Gudmundsd\u00f3ttir", "given": "J\u00f3n\u00edna S", "initials": "JS", "orcid": "0000-0002-4500-4078", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd10ee75400d497a8d1c5b9ac7fccdc7.json"}}, {"family": "Douglass", "given": "Martin V", "initials": "MV"}, {"family": "Trent", "given": "M Stephen", "initials": "MS", "orcid": "0000-0001-6134-1800", "researcher": {"href": "https://publications.scilifelab.se/researcher/009aef5966e64414a03b8bb67351dff8.json"}}, {"family": "Andersson", "given": "Dan I", "initials": "DI", "orcid": "0000-0001-6640-2174", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb042b3dfa21450e862a29951ea0c1eb.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "17", "issue": "1", "pages": "e1009227", "issn-l": "1553-7390"}, "abstract": "Antibiotic resistance is a rapidly increasing medical problem that severely limits the success of antibiotic treatments, and the identification of resistance determinants is key for surveillance and control of resistance dissemination. Horizontal transfer is the dominant mechanism for spread of resistance genes between bacteria but little is known about the original emergence of resistance genes. Here, we examined experimentally if random sequences can generate novel antibiotic resistance determinants de novo. By utilizing highly diverse expression libraries encoding random sequences to select for open reading frames that confer resistance to the last-resort antibiotic colistin in Escherichia coli, six de novo colistin resistance conferring peptides (Dcr) were identified. The peptides act via direct interactions with the sensor kinase PmrB (also termed BasS in E. coli), causing an activation of the PmrAB two-component system (TCS), modification of the lipid A domain of lipopolysaccharide and subsequent colistin resistance. This kinase-activation was extended to other TCS by generation of chimeric sensor kinases. Our results demonstrate that peptides with novel activities mediated via specific peptide-protein interactions in the transmembrane domain of a sensory transducer can be selected de novo, suggesting that the origination of such peptides from non-coding regions is conceivable. In addition, we identified a novel class of resistance determinants for a key antibiotic that is used as a last resort treatment for several significant pathogens. The high-level resistance provided at low expression levels, absence of significant growth defects and the functionality of Dcr peptides across different genera suggest that this class of peptides could potentially evolve as bona fide resistance determinants in natura.", "doi": "10.1371/journal.pgen.1009227", "pmid": "33411736", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7790251"}, {"db": "pii", "key": "PGENETICS-D-20-01241"}], "notes": [], "created": "2023-03-07T14:36:24.716Z", "modified": "2024-01-16T13:46:30.935Z"}, {"entity": "publication", "iuid": "daf757c012d548dd8bcf520909fc90d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/daf757c012d548dd8bcf520909fc90d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/daf757c012d548dd8bcf520909fc90d5"}}, "title": "Evolution of a New Function by Fusion between Phage DNA and a Bacterial Gene.", "authors": [{"family": "Warsi", "given": "Omar", "initials": "O"}, {"family": "Knopp", "given": "Michael", "initials": "M", "orcid": "0000-0002-8218-3263", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2620cb646745b892428f758597f78e.json"}}, {"family": "Surkov", "given": "Serhiy", "initials": "S"}, {"family": "Jerlstr\u00f6m Hultqvist", "given": "Jon", "initials": "J"}, {"family": "Andersson", "given": "Dan I", "initials": "DI"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "5", "pages": "1329-1341", "issn-l": "0737-4038"}, "abstract": "Mobile genetic elements, such as plasmids, phages, and transposons, are important sources for evolution of novel functions. In this study, we performed a large-scale screening of metagenomic phage libraries for their ability to suppress temperature-sensitivity in Salmonella enterica serovar Typhimurium strain LT2 mutants to examine how phage DNA could confer evolutionary novelty to bacteria. We identified an insert encoding 23 amino acids from a phage that when fused with a bacterial DNA-binding repressor protein (LacI) resulted in the formation of a chimeric protein that localized to the outer membrane. This relocalization of the chimeric protein resulted in increased membrane vesicle formation and an associated suppression of the temperature sensitivity of the bacterium. Both the host LacI protein and the extracellular 23-amino acid stretch are necessary for the generation of the novel phenotype. Furthermore, mutational analysis of the chimeric protein showed that although the native repressor function of the LacI protein is maintained in this chimeric structure, it is not necessary for the new function. Thus, our study demonstrates how a gene fusion between foreign DNA and bacterial DNA can generate novelty without compromising the native function of a given gene.", "doi": "10.1093/molbev/msaa007", "pmid": "31977019", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "5707441"}, {"db": "pmc", "key": "PMC7182210"}], "notes": [], "created": "2020-01-30T15:58:41.118Z", "modified": "2024-01-16T13:46:30.952Z"}]}