{"entity": "researcher", "timestamp": "2026-10-05T21:37:35.271Z", "family": "Thoma", "given": "Johannes", "initials": "J", "orcid": "0000-0003-3584-8274", "affiliations": ["Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 G\u00f6teborg, Sweden.", "Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 G\u00f6teborg, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/98d27ad4d2224fbaa840469f85a596e4.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/98d27ad4d2224fbaa840469f85a596e4"}}, "publications": [{"entity": "publication", "iuid": "1ff43766eb154a0eaf667914e8c3c386", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ff43766eb154a0eaf667914e8c3c386.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ff43766eb154a0eaf667914e8c3c386"}}, "title": "Marine-Inspired Antimicrobial Peptides Disrupt Gene Expression at the DNA Level.", "authors": [{"family": "Beyer", "given": "Luisa I", "initials": "LI"}, {"family": "Thoma", "given": "Johannes", "initials": "J", "orcid": "0000-0003-3584-8274", "researcher": {"href": "https://publications.scilifelab.se/researcher/98d27ad4d2224fbaa840469f85a596e4.json"}}, {"family": "Acha Alarcon", "given": "Leonarda", "initials": "L", "orcid": "0000-0002-9453-7479", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fa254340a5b4ec39809654b54fd3481.json"}}, {"family": "Unksov", "given": "Ivan N", "initials": "IN"}, {"family": "Karlsson", "given": "Roger", "initials": "R"}, {"family": "Inda-D\u00edaz", "given": "Juan S", "initials": "JS"}, {"family": "Tietze", "given": "Alesia A", "initials": "AA", "orcid": "0000-0002-9281-548X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c9c55ec11d84630a4b4472cd21ef96b.json"}}], "type": "journal article", "published": "2026-01-09", "journal": {"title": "ACS Infect Dis", "issn": "2373-8227", "volume": "12", "issue": "1", "pages": "447-459", "issn-l": null}, "abstract": "Genome mining of Streptomyces sp. H-KF8 combined with sequence engineering yielded two serum-stable, noncytotoxic, nonlytic antimicrobial peptides, L3 and L3-K. Initial studies in uropathogenic Escherichia coli suggested membrane effects and nucleoid relaxation, prompting a comprehensive investigation of their mode of action. In this study tandem mass tag (TMT)-based quantitative proteomics revealed extensive proteome remodeling, with 175 and 120 differentially expressed proteins (DEPs) after treatment with L3 and L3-K, respectively. L3 induced predominantly upregulated responses linked to metabolism, RNA processing, transport, and homeostasis, whereas L3-K mainly caused the downregulation of proteins involved in metabolism, transport, and cell structure. Both peptides disrupted ABC transporter-mediated nutrient uptake and elicited stress responses, while L3 specifically perturbed the mal regulon, indicative of broader transcriptional dysregulation. Complementary fluorescent dye displacement and in vitro transcription/translation assays demonstrated nonspecific DNA binding, stronger for L3 than L3-K, and potent inhibition of transcriptional and translational processes. Strikingly, inhibitory concentrations paralleled their minimum inhibitory concentrations, directly linking DNA binding and interference with central information processing to antimicrobial activity. These findings reveal that L3 and L3-K primarily act by targeting DNA and interfering with the transcription-translation machinery. Beyond offering mechanistic insights, this study underscores peptides' potential to act as scaffolds for next-generation antimicrobial peptides with DNA-binding and nonmembrane-lytic activity.", "doi": "10.1021/acsinfecdis.5c01000", "pmid": "41363146", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12797237"}], "notes": [], "created": "2026-01-27T13:32:34.240Z", "modified": "2026-01-27T13:32:34.344Z"}, {"entity": "publication", "iuid": "bbbef057569645bdafa2067f2ae47efc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bbbef057569645bdafa2067f2ae47efc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bbbef057569645bdafa2067f2ae47efc"}}, "title": "Structural basis of DegP protease temperature-dependent activation.", "authors": [{"family": "\u0160ulskis", "given": "Darius", "initials": "D", "orcid": "0000-0002-6925-4469", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f96dc2852dc41dd93310a4e33d3c216.json"}}, {"family": "Thoma", "given": "Johannes", "initials": "J", "orcid": "0000-0003-3584-8274", "researcher": {"href": "https://publications.scilifelab.se/researcher/98d27ad4d2224fbaa840469f85a596e4.json"}}, {"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM", "orcid": "0000-0002-3135-7964", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a6d61fc1a64677874973c3247b1eb4.json"}}], "type": "journal article", "published": "2021-12-10", "journal": {"title": "Sci Adv", "issn": "2375-2548", "issn-l": "2375-2548", "volume": "7", "issue": "50", "pages": "eabj1816"}, "abstract": "Protein quality control is an essential cellular function mainly executed by a vast array of different proteases and molecular chaperones. One of the bacterial high temperature requirement A (HtrA) protein family members, the homo-oligomeric DegP protease, plays a crucial role in the Escherichia coli protein quality control machinery by removing unfolded proteins or preventing their aggregation and chaperoning them to their final folded state within the periplasm. DegP contains two regulatory PDZ domains, which play key roles in substrate recognition and in the transformation of DegP between inactive hexameric and proteolytic active cage-like structures. Here, we analyze the interaction and dynamics of the DegP PDZ domains underlying this transformation by high-resolution NMR spectroscopy complemented with biochemical cleavage assays. We identify an interdomain molecular lock, which controls the interactions between the two PDZ domains, regulated by fine-tuned temperature-dependent protein dynamics, and which is potentially conserved in proteins harboring tandem PDZ domains.", "doi": "10.1126/sciadv.abj1816", "pmid": "34878848", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8654288"}], "notes": [], "created": "2020-12-11T09:06:12.338Z", "modified": "2025-10-17T13:03:55.266Z"}]}