{"entity": "journal", "iuid": "de7d338eb30a4938ac5eac44dc062c2f", "timestamp": "2026-07-14T03:22:42.839Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/ACS%20Infect%20Dis.json"}, "display": {"href": "https://publications.scilifelab.se/journal/ACS%20Infect%20Dis"}}, "title": "ACS Infect Dis", "issn": "2373-8227", "issn-l": null, "publications_count": 4, "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": "c5f05c63059c46de86c8967dcca74802", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c5f05c63059c46de86c8967dcca74802.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c5f05c63059c46de86c8967dcca74802"}}, "title": "Mimicking Nonribosomal Peptides from the Marine Actinomycete Streptomyces sp. H-KF8 Leads to Antimicrobial Peptides.", "authors": [{"family": "Beyer", "given": "Luisa I", "initials": "LI"}, {"family": "Sch\u00e4fer", "given": "Ann-Britt", "initials": "AB"}, {"family": "Undabarrena", "given": "Agustina", "initials": "A"}, {"family": "Mattsby-Baltzer", "given": "Inger", "initials": "I"}, {"family": "Tietze", "given": "Daniel", "initials": "D", "orcid": "0000-0002-9251-1902", "researcher": {"href": "https://publications.scilifelab.se/researcher/c25c1c818e8a43039bdbbb7a376db42d.json"}}, {"family": "Svensson", "given": "Elin", "initials": "E"}, {"family": "Stubelius", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-4170-8892", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fd7733c962540e9b759ba6a90af42b5.json"}}, {"family": "Wenzel", "given": "Michaela", "initials": "M", "orcid": "0000-0001-9969-6113", "researcher": {"href": "https://publications.scilifelab.se/researcher/89a2267fffda4a7e8d30023ae5d75121.json"}}, {"family": "C\u00e1mara", "given": "Beatriz", "initials": "B"}, {"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": "2024-01-12", "journal": {"title": "ACS Infect Dis", "issn": "2373-8227", "volume": "10", "issue": "1", "pages": "79-92", "issn-l": null}, "abstract": "Microorganisms within the marine environment have been shown to be very effective sources of naturally produced antimicrobial peptides (AMPs). Several nonribosomal peptides were identified based on genome mining predictions of Streptomyces sp. H-KF8, a marine Actinomycetota isolated from a remote Northern Chilean Patagonian fjord. Based on these predictions, a series of eight peptides, including cyclic peptides, were designed and chemically synthesized. Six of these peptides showed antimicrobial activity. Mode of action studies suggest that two of these peptides potentially act on the cell membrane via a novel mechanism allowing the passage of small ions, resulting in the dissipation of the membrane potential. This study shows that though structurally similar peptides, determined by NMR spectroscopy, the incorporation of small sequence mutations results in a dramatic influence on their bioactivity including mode of action. The qualified hit sequence can serve as a basis for more potent AMPs in future studies.", "doi": "10.1021/acsinfecdis.3c00206", "pmid": "38113038", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10788856"}], "notes": [], "created": "2025-11-27T08:14:21.224Z", "modified": "2025-11-27T08:14:21.522Z"}, {"entity": "publication", "iuid": "c0c0048885944b84a524ece147e977f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0c0048885944b84a524ece147e977f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0c0048885944b84a524ece147e977f4"}}, "title": "In Vitro and In Vivo Development of a \u03b2-Lactam-Metallo-\u03b2-Lactamase Inhibitor: Targeting Carbapenem-Resistant Enterobacterales.", "authors": [{"family": "Peters", "given": "Byron K", "initials": "BK", "orcid": "0000-0003-2889-1354", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbb194a36bfa4a8ca6203ddc5063d033.json"}}, {"family": "Reddy", "given": "Nakita", "initials": "N"}, {"family": "Shungube", "given": "Mbongeni", "initials": "M"}, {"family": "Girdhari", "given": "Letisha", "initials": "L"}, {"family": "Baijnath", "given": "Sooraj", "initials": "S"}, {"family": "Mdanda", "given": "Sipho", "initials": "S"}, {"family": "Chetty", "given": "Lloyd", "initials": "L"}, {"family": "Ntombela", "given": "Thandokuhle", "initials": "T"}, {"family": "Arumugam", "given": "Thilona", "initials": "T"}, {"family": "Bester", "given": "Linda A", "initials": "LA"}, {"family": "Singh", "given": "Sanil D", "initials": "SD"}, {"family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "researcher": {"href": "https://publications.scilifelab.se/researcher/f96bfd695ee44484ad9b87f9ef4e76a0.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI"}, {"family": "Maguire", "given": "Glenn E M", "initials": "GEM"}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}], "type": "journal article", "published": "2023-03-10", "journal": {"title": "ACS Infect Dis", "issn": "2373-8227", "issn-l": null, "volume": "9", "issue": "3", "pages": "486-496"}, "abstract": "\u03b2-lactams are the most prescribed class of antibiotics due to their potent, broad-spectrum antimicrobial activities. However, alarming rates of antimicrobial resistance now threaten the clinical relevance of these drugs, especially for the carbapenem-resistant Enterobacterales expressing metallo-\u03b2-lactamases (MBLs). Antimicrobial agents that specifically target these enzymes to restore the efficacy of last resort \u03b2-lactam drugs, that is, carbapenems, are therefore desperately needed. Herein, we present a cyclic zinc chelator covalently attached to a \u03b2-lactam scaffold (cephalosporin), that is, BP1. Observations from in vitro assays (with seven MBL expressing bacteria from different geographies) have indicated that BP1 restored the efficacy of meropenem to \u2264 0.5 mg/L, with sterilizing activity occurring from 8 h postinoculation. Furthermore, BP1 was nontoxic against human hepatocarcinoma cells (IC50 > 1000 mg/L) and exhibited a potency of (K) 24.8 and 97.4 \u03bcM against Verona integron-encoded MBL (VIM-2) and New Delhi metallo \u03b2-lactamase (NDM-1), respectively. There was no inhibition observed from BP1 with the human zinc-containing enzyme glyoxylase II up to 500 \u03bcM. Preliminary molecular docking of BP1 with NDM-1 and VIM-2 sheds light on BP1's mode of action. In iappKlebsiella pneumoniae NDM infected mice, BP1 coadministered with meropenem was efficacious in reducing the bacterial load by >3 log10 units' postinfection. The findings herein propose a favorable therapeutic combination strategy that restores the activity of the carbapenem antibiotic class and complements the few MBL inhibitors under development, with the ultimate goal of curbing antimicrobial resistance.", "doi": "10.1021/acsinfecdis.2c00485", "pmid": "36786013", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10012271"}], "notes": [], "created": "2023-05-15T15:31:08.266Z", "modified": "2025-10-17T13:05:07.655Z"}, {"entity": "publication", "iuid": "0a0683ca8ff9405aac1f62a0bbc2e8ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0a0683ca8ff9405aac1f62a0bbc2e8ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0a0683ca8ff9405aac1f62a0bbc2e8ad"}}, "title": "Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity.", "authors": [{"family": "Samuelsson", "given": "Ebba", "initials": "E"}, {"family": "Mirgorodskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Nystr\u00f6m", "given": "Kristina", "initials": "K"}, {"family": "B\u00e4ckstr\u00f6m", "given": "Malin", "initials": "M"}, {"family": "Liljeqvist", "given": "Jan-\u00c5ke", "initials": "J\u00c5"}, {"family": "Nord\u00e9n", "given": "Rickard", "initials": "R", "orcid": "0000-0002-3866-7228", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c66bccaf8ae455996d71c1ca02011db.json"}}], "type": "journal article", "published": "2022-09-09", "journal": {"title": "ACS Infect Dis", "issn": "2373-8227", "issn-l": null, "volume": "8", "issue": "9", "pages": "1883-1893"}, "abstract": "The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins.", "doi": "10.1021/acsinfecdis.2c00155", "pmid": "35980012", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9469093"}], "notes": [], "created": "2022-10-04T13:47:09.329Z", "modified": "2024-01-16T13:46:28.445Z"}], "created": "2022-10-04T13:47:09.387Z", "modified": "2022-10-04T13:47:09.387Z"}