{"entity": "journal", "iuid": "779298711bcc4135babd4a18900a62f5", "timestamp": "2026-07-15T17:01:37.849Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Antimicrob.%20Agents%20Chemother..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Antimicrob.%20Agents%20Chemother."}}, "title": "Antimicrob. Agents Chemother.", "issn": "1098-6596", "issn-l": "0066-4804", "publications_count": 11, "publications": [{"entity": "publication", "iuid": "de0ae51b949548c0832c9967b8f4a1a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/de0ae51b949548c0832c9967b8f4a1a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/de0ae51b949548c0832c9967b8f4a1a6"}}, "title": "Extended-Spectrum-\u03b2-Lactamase- and Plasmid AmpC-Producing Escherichia coli Causing Community-Onset Bloodstream Infection: Association of Bacterial Clones and Virulence Genes with Septic Shock, Source of Infection, and Recurrence.", "authors": [{"family": "Fr\u00f6ding", "given": "Inga", "initials": "I"}, {"family": "Hasan", "given": "Badrul", "initials": "B"}, {"family": "Sylvin", "given": "Isak", "initials": "I"}, {"family": "Coorens", "given": "Maarten", "initials": "M"}, {"family": "Naucl\u00e9r", "given": "Pontus", "initials": "P"}, {"family": "Giske", "given": "Christian G", "initials": "CG"}], "type": "journal article", "published": "2020-07-22", "journal": {"title": "Antimicrob. Agents Chemother.", "issn": "1098-6596", "volume": "64", "issue": "8", "issn-l": "0066-4804"}, "abstract": "Invasive infections due to extended-spectrum-\u03b2-lactamase- and pAmpC-producing Escherichia coli (ESBL/pAmpC-EC) are an important cause of morbidity, often caused by the high-risk clone sequence type (ST131) and isolates classified as extraintestinal pathogenic E. coli (ExPEC). The relative influence of host immunocompetence versus microbiological virulence factors in the acquisition and outcome of bloodstream infections (BSI) is poorly understood. Herein, we used whole-genome sequencing on 278 blood culture isolates of ESBL/pAmpC-EC from 260 patients with community-onset BSI collected from 2012 to 2015 in Stockholm to study the association of virulence genes, sequence types, and antimicrobial resistance with severity of disease, infection source, ESBL/pAmpC-EC BSI low-risk patients, and patients with repeated episodes. ST131 subclade C2 comprised 29% of all patients. Factors associated with septic shock in multivariable analysis were patient host factors (hematologic cancer or transplantation and reduced daily living activity), presence of the E. coli virulence factor iss (increased serum survival), absence of phenotypic multidrug resistance, and absence of the genes pap and hsp Adhesins, particularly pap, were associated with urinary tract infection (UTI) source, while isolates from post-prostate biopsy sepsis had a low overall number of virulence operons, including adhesins, and commonly belonged to ST131 clades A, B, and subclade C1, ST1193, and ST648. ST131 was associated with recurrent episodes. In conclusion, the most interesting finding is the association of iss with septic shock. Adhesins are important for UTI pathogenesis, while otherwise low-pathogenic isolates from the microbiota can cause post-prostate biopsy sepsis.", "doi": "10.1128/AAC.02351-19", "pmid": "32423949", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "AAC.02351-19"}, {"db": "pmc", "key": "PMC7526827"}], "notes": [], "created": "2020-06-01T09:13:35.267Z", "modified": "2021-11-10T12:50:56.968Z"}, {"entity": "publication", "iuid": "bea2a6c152d74b7a8b9703f4e41bfb79", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bea2a6c152d74b7a8b9703f4e41bfb79.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bea2a6c152d74b7a8b9703f4e41bfb79"}}, "title": "Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV.", "authors": [{"family": "Sundell", "given": "Jesper", "initials": "J", "orcid": "0000-0002-5395-9819", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dba5ed8dd254a5b9f09cb89f3dda721.json"}}, {"family": "Bienvenu", "given": "Emile", "initials": "E"}, {"family": "Birgersson", "given": "Sofia", "initials": "S"}, {"family": "\u00c4bel\u00f6", "given": "Angela", "initials": "A"}, {"family": "Ashton", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2020-01-27", "journal": {"title": "Antimicrob. Agents Chemother.", "issn": "1098-6596", "issn-l": "0066-4804", "volume": "64", "issue": "2", "pages": null}, "abstract": "This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling. A one-compartment disposition model with first-order elimination and four transit compartments prior to first-order absorption was found to adequately describe the concentration-time profiles of ethambutol in plasma. Body weight was implemented as an allometric function on the clearance and volume parameters. Estimates of oral clearance and volume of distribution were 77.4 liters/h and 76.2 liters, respectively. A G/A mutation with regard to CYP1A2 2159 G>A was associated with a 50% reduction in relative bioavailability. Simulations revealed that doses of 30 mg/kg of body weight and 50 mg/kg for G/G and G/A carriers, respectively, would result in clinically adequate exposure. The results presented here suggest that CYP1A2 polymorphism affects ethambutol exposure in this population and that current treatment guidelines may result in underexposure in patients coinfected with tuberculosis and HIV. Based on simulations, a dose increase from15 to 20 mg/kg to 30 mg/kg is suggested. However, the 50-mg/kg dose required to reach therapeutic exposure in G/A carriers may be inappropriate due to the dose-dependent toxicity of ethambutol. Additional studies are required to further investigate CYP450 polymorphism effects on ethambutol pharmacokinetics.", "doi": "10.1128/AAC.01583-19", "pmid": "31712201", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "AAC.01583-19"}, {"db": "pmc", "key": "PMC6985744"}], "notes": [], "created": "2021-01-14T11:59:21.203Z", "modified": "2021-12-07T13:56:13.923Z"}, {"entity": "publication", "iuid": "e9f557da08bf419cb38c679f6c5b98b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9f557da08bf419cb38c679f6c5b98b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9f557da08bf419cb38c679f6c5b98b8"}}, "title": "Upregulation of PBP1B and LpoB in cysB Mutants Confers Mecillinam (Amdinocillin) Resistance in Escherichia coli.", "authors": [{"family": "Thulin", "given": "Elisabeth", "initials": "E"}, {"family": "Andersson", "given": "Dan I", "initials": "DI"}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Antimicrob. Agents Chemother.", "issn": "1098-6596", "volume": "63", "issue": "10", "issn-l": "0066-4804"}, "abstract": "Mecillinam (amdinocillin) is a \u03b2-lactam antibiotic that inhibits the essential penicillin-binding protein 2 (PBP2). In clinical isolates of Escherichia coli from urinary tract infections, inactivation of the cysB gene (which encodes the main regulator of cysteine biosynthesis, CysB) is the major cause of resistance. How a nonfunctional CysB protein confers resistance is unknown, however, and in this study we wanted to examine the mechanism of resistance. Results show that cysB mutations cause a gene regulatory response that changes the expression of \u223c450 genes. Among the proteins that show increased levels are the PBP1B, LpoB, and FtsZ proteins, which are known to be involved in peptidoglycan biosynthesis. Artificial overexpression of either PBP1B or LpoB in a wild-type E. coli strain conferred mecillinam resistance; conversely, inactivation of either the mrcB gene (which encodes PBP1B) or the lpoB gene (which encodes the PBP1B activator LpoB) made cysB mutants susceptible. These results show that expression of the proteins PBP1B and LpoB is both necessary and sufficient to confer mecillinam resistance. The addition of reducing agents to a cysB mutant converted it to full susceptibility, with associated downregulation of PBP1B, LpoB, and FtsZ. We propose a model in which cysB mutants confer mecillinam resistance by inducing a response that causes upregulation of the PBP1B and LpoB proteins. The higher levels of these two proteins can then rescue cells with mecillinam-inhibited PBP2. Our results also show how resistance can be modulated by external conditions such as reducing agents.", "doi": "10.1128/AAC.00612-19", "pmid": "31332059", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "AAC.00612-19"}, {"db": "pmc", "key": "PMC6761508"}], "notes": [], "created": "2020-01-30T15:58:47.127Z", "modified": "2024-01-16T13:46:31.568Z"}, {"entity": "publication", "iuid": "9f280eda9bb5412da6e1ee908e970fbf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f280eda9bb5412da6e1ee908e970fbf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f280eda9bb5412da6e1ee908e970fbf"}}, "title": "Dynamics of Resistance Plasmids in Extended-Spectrum-\u03b2-Lactamase-Producing Enterobacteriaceae during Postinfection Colonization.", "authors": [{"family": "Brolund", "given": "Alma", "initials": "A"}, {"family": "Rajer", "given": "Fredrika", "initials": "F", "orcid": "0000-0002-4211-5696", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab140cb43f3b4ecfb1e525f92f3445d3.json"}}, {"family": "Giske", "given": "Christian G", "initials": "CG"}, {"family": "Melefors", "given": "\u00d6jar", "initials": "\u00d6"}, {"family": "Titelman", "given": "Emilia", "initials": "E"}, {"family": "Sandegren", "given": "Linus", "initials": "L", "orcid": "0000-0001-7382-9782", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f0b60050f1c44eca1dc5adb1141ecc5.json"}}], "type": "journal article", "published": "2019-04-00", "journal": {"volume": "63", "issn": "1098-6596", "issue": "4", "pages": null, "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "Extended-spectrum \u03b2-lactamase-producing Enterobacteriaceae (EPE) are a major cause of bloodstream infections, and the colonization rate of EPE in the gut microbiota of individuals lacking prior hospitalization or comorbidities is increasing. In this study, we performed an in-depth investigation of the temporal dynamics of EPE and their plasmids during one year by collecting fecal samples from three patients initially seeking medical care for urinary tract infections. In two of the patients, the same strain that caused the urinary tract infection (UTI) was found at all consecutive samplings from the gut microbiota, and no other EPEs were detected, while in the third patient the UTI strain was only found in the initial UTI sample. Instead, this patient presented a complex situation where a mixed microbiota of different EPE strain types, including three different E. coli ST131 variants, as well as different bacterial species, was identified over the course of the study. Different plasmid dynamics were displayed in each of the patients, including the spread of plasmids between different strain types over time and the transposition of blaCTX-M-15 from the chromosome to a plasmid, followed by subsequent loss through homologous recombination. Small cryptic plasmids were found in all isolates from all patients, and they appear to move frequently between different strains in the microbiota. In conclusion, we could demonstrate an extensive variation of EPE strain types, plasmid composition, rearrangements, and horizontal gene transfer of genetic material illustrating the high dynamics nature and interactive environment of the gut microbiota during post-UTI carriage.", "doi": "10.1128/AAC.02201-18", "pmid": "30745391", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "AAC.02201-18"}, {"db": "pmc", "key": "PMC6437490"}], "notes": [], "created": "2019-11-25T14:05:38.568Z", "modified": "2021-06-21T13:33:55.310Z"}, {"entity": "publication", "iuid": "66d129fdaa424216a637ee29b4d4255b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/66d129fdaa424216a637ee29b4d4255b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/66d129fdaa424216a637ee29b4d4255b"}}, "title": "N-Acylated Derivatives of Sulfamethoxazole Block Chlamydia Fatty Acid Synthesis and Interact with FabF.", "authors": [{"family": "Mojica", "given": "Sergio A", "initials": "SA"}, {"family": "Salin", "given": "Olli", "initials": "O"}, {"family": "Bastidas", "given": "Robert J", "initials": "RJ"}, {"family": "Sunduru", "given": "Naresh", "initials": "N"}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Andersson", "given": "C David", "initials": "CD"}, {"family": "N\u00fa\u00f1ez-Otero", "given": "Carlos", "initials": "C"}, {"family": "Engstr\u00f6m", "given": "Patrik", "initials": "P"}, {"family": "Valdivia", "given": "Raphael H", "initials": "RH"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}, {"family": "Gylfe", "given": "\u00c5sa", "initials": "\u00c5"}], "type": "journal article", "published": "2017-10-00", "journal": {"volume": "61", "issn": "1098-6596", "issue": "10", "pages": "e00716-17", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway is indispensable for Chlamydia growth. Previously, a high-content screen with Chlamydia trachomatis-infected cells was performed, and acylated sulfonamides were identified to be potent growth inhibitors of the bacteria. C. trachomatis strains resistant to acylated sulfonamides were isolated by serial passage of a wild-type strain in the presence of low compound concentrations. Results from whole-genome sequencing of 10 isolates from two independent drug-resistant populations revealed that mutations that accumulated in fabF were predominant. Studies of the interaction between the FabF protein and small molecules showed that acylated sulfonamides directly bind to recombinant FabF in vitro and treatment of C. trachomatis-infected HeLa cells with the compounds leads to a decrease in the synthesis of Chlamydia fatty acids. This work demonstrates the importance of FASII for Chlamydia development and may lead to the development of new antimicrobials.", "doi": "10.1128/AAC.00716-17", "pmid": "28784680", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.00716-17"}, {"db": "pmc", "key": "PMC5610512"}], "notes": [], "created": "2017-10-31T12:05:28.123Z", "modified": "2025-10-17T13:03:59.574Z"}, {"entity": "publication", "iuid": "c99e43d2fa8f4d019e121509ac8b495a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c99e43d2fa8f4d019e121509ac8b495a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c99e43d2fa8f4d019e121509ac8b495a"}}, "title": "The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents.", "authors": [{"family": "Bengtsson-Palme", "given": "Johan", "initials": "J"}, {"family": "Angelin", "given": "Martin", "initials": "M"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Kjellqvist", "given": "Sanela", "initials": "S"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Palmgren", "given": "Helena", "initials": "H"}, {"family": "Larsson", "given": "D G Joakim", "initials": "DGJ"}, {"family": "Johansson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2015-10-00", "journal": {"volume": "59", "issn": "1098-6596", "issue": "10", "pages": "6551-6560", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.", "doi": "10.1128/AAC.00933-15", "pmid": "26259788", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.00933-15"}, {"db": "pmc", "key": "PMC4576037"}], "notes": [], "created": "2017-05-02T12:56:34.308Z", "modified": "2020-01-21T13:53:21.177Z"}, {"entity": "publication", "iuid": "680c61c3b7e842d8ba4bc1341889405d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/680c61c3b7e842d8ba4bc1341889405d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/680c61c3b7e842d8ba4bc1341889405d"}}, "title": "Screening for inhibition of Vibrio cholerae VipA-VipB interaction identifies small-molecule compounds active against type VI secretion.", "authors": [{"family": "Sun", "given": "Kun", "initials": "K"}, {"family": "Br\u00f6ms", "given": "Jeanette", "initials": "J"}, {"family": "Lavander", "given": "Moa", "initials": "M"}, {"family": "Gurram", "given": "Bharat Kumar", "initials": "BK"}, {"family": "Enquist", "given": "Per-Anders", "initials": "P"}, {"family": "Andersson", "given": "C David", "initials": "CD"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}, {"family": "Sj\u00f6stedt", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2014-07-00", "journal": {"volume": "58", "issn": "1098-6596", "issue": "7", "pages": "4123-4130", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an \u03b1-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance.", "doi": "10.1128/AAC.02819-13", "pmid": "24798289", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.02819-13"}, {"db": "pmc", "key": "PMC4068513"}, {"db": "GENBANK", "key": "KJ735588"}, {"db": "GENBANK", "key": "KJ735589"}], "notes": "Laboratories for Chemical Biology Ume\u00e5 (LCBU)", "created": "2017-05-04T14:56:41.143Z", "modified": "2025-10-17T13:04:29.975Z"}, {"entity": "publication", "iuid": "ab0f2c106da846a7a02c4beb2b207469", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ab0f2c106da846a7a02c4beb2b207469.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ab0f2c106da846a7a02c4beb2b207469"}}, "title": "N-acylated derivatives of sulfamethoxazole and sulfafurazole inhibit intracellular growth of Chlamydia trachomatis.", "authors": [{"family": "Marwaha", "given": "Sania", "initials": "S"}, {"family": "Uvell", "given": "Hanna", "initials": "H"}, {"family": "Salin", "given": "Olli", "initials": "O"}, {"family": "Lindgren", "given": "Anders E G", "initials": "AEG"}, {"family": "Silver", "given": "Jim", "initials": "J"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}, {"family": "Gylfe", "given": "Asa", "initials": "A"}], "type": "journal article", "published": "2014-05-00", "journal": {"volume": "58", "issn": "1098-6596", "issue": "5", "pages": "2968-2971", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "Antibacterial compounds with novel modes of action are needed for management of bacterial infections. Here we describe a high-content screen of 9,800 compounds identifying acylated sulfonamides as novel growth inhibitors of the sexually transmitted pathogen Chlamydia trachomatis. The effect was bactericidal and distinct from that of sulfonamide antibiotics, as para-aminobenzoic acid did not reduce efficacy. Chemical inhibitors play an important role in Chlamydia research as probes of potential targets and as drug development starting points.", "doi": "10.1128/AAC.02015-13", "pmid": "24566180", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.02015-13"}, {"db": "pmc", "key": "PMC3993265"}], "notes": "Laboratories for Chemical Biology Ume\u00e5 (LCBU)", "created": "2017-05-04T14:56:41.445Z", "modified": "2025-10-17T13:04:30.067Z"}, {"entity": "publication", "iuid": "13eb2eee89584305aab1e955570e23b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/13eb2eee89584305aab1e955570e23b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/13eb2eee89584305aab1e955570e23b3"}}, "title": "In vitro and in vivo activities of 2-aminopyrazines and 2-aminopyridines in experimental models of human African trypanosomiasis.", "authors": [{"family": "Vodnala", "given": "Suman K", "initials": "SK"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Sj\u00f6berg", "given": "Birger", "initials": "B"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Rottenberg", "given": "Martin E", "initials": "ME"}, {"family": "Hammarstr\u00f6m", "given": "Lars G J", "initials": "LGJ"}], "type": "journal article", "published": "2013-02-00", "journal": {"volume": "57", "issn": "1098-6596", "issue": "2", "pages": "1012-1018", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "New drugs for the treatment of human African trypanosomiasis are urgently needed. A number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for Trypanosoma brucei subsp. brucei viability. Described compounds are trypanotoxic in the submicromolar range and show comparably low cytotoxicity on representative mammalian cell lines. Specifically, 6-([6-fluoro-3,4-dihydro-2H-1-benzopyran-4-yl)]oxy)-N-(piperidin-4-yl)pyrazin-2-amine (CBK201352) is trypanotoxic for T. brucei subsp. brucei, T. brucei subsp. gambiense, and T. brucei subsp. rhodesiense and is nontoxic to mammalian cell lines, and in vitro preclinical assays predict promising pharmacokinetic parameters. Mice inoculated intraperitoneally (i.p.) with 25 mg/kg CBK201352 twice daily for 10 days, starting on the day of infection with T. brucei subsp. brucei, show complete clearance of parasites for more than 90 days. Thus, CBK201352 and related analogs are promising leads for the development of novel treatments for human African trypanosomiasis.", "doi": "10.1128/AAC.01870-12", "pmid": "23254423", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.01870-12"}, {"db": "pmc", "key": "PMC3553678"}], "notes": "Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)\r\nADME of Therapeutics (UDOPP)", "created": "2017-05-04T14:56:46.506Z", "modified": "2025-10-17T13:04:30.435Z"}, {"entity": "publication", "iuid": "5a6dbca9181a46b196d824946987c4bf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5a6dbca9181a46b196d824946987c4bf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5a6dbca9181a46b196d824946987c4bf"}}, "title": "2-[4,5-Difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, an antiviral compound with activity against acyclovir-resistant isolates of herpes simplex virus types 1 and 2.", "authors": [{"family": "Strand", "given": "M\u00e5rten", "initials": "M"}, {"family": "Islam", "given": "Koushikul", "initials": "K"}, {"family": "Edlund", "given": "Karin", "initials": "K"}, {"family": "Oberg", "given": "Christopher T", "initials": "CT"}, {"family": "Allard", "given": "Annika", "initials": "A"}, {"family": "Bergstr\u00f6m", "given": "Tomas", "initials": "T"}, {"family": "Mei", "given": "Ya-Fang", "initials": "Y"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}, {"family": "Wadell", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2012-11-00", "journal": {"volume": "56", "issn": "1098-6596", "issue": "11", "pages": "5735-5743", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are responsible for lifelong latent infections in humans, with periods of viral reactivation associated with recurring ulcerations in the orofacial and genital tracts. In immunosuppressed patients and neonates, HSV infections are associated with severe morbidity and, in some cases, even mortality. Today, acyclovir is the standard therapy for the management of HSV infections. However, the need for novel antiviral agents is apparent, since HSV isolates resistant to acyclovir therapy are frequently isolated in immunosuppressed patients. In this study, we assessed the anti-HSV activity of the antiadenoviral compounds 2-[2-(2-benzoylamino)-benzoylamino]benzoic acid (benzavir-1) and 2-[4,5-difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid (benzavir-2) on HSV-1 and HSV-2. Both compounds were active against both viruses. Importantly, benzavir-2 had potency similar to that of acyclovir against both HSV types, and it was active against clinical acyclovir-resistant HSV isolates.", "doi": "10.1128/AAC.01072-12", "pmid": "22908173", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.01072-12"}, {"db": "pmc", "key": "PMC3486576"}], "notes": "Laboratories for Chemical Biology Ume\u00e5 (LCBU)", "created": "2017-05-04T14:56:38.223Z", "modified": "2025-10-17T13:04:30.508Z"}, {"entity": "publication", "iuid": "8ee4600e144f43e38d5812d0b02725f0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8ee4600e144f43e38d5812d0b02725f0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8ee4600e144f43e38d5812d0b02725f0"}}, "title": "Small-molecule screening using a whole-cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel antiadenoviral compound.", "authors": [{"family": "Andersson", "given": "Emma K", "initials": "EK"}, {"family": "Strand", "given": "M\u00e5rten", "initials": "M"}, {"family": "Edlund", "given": "Karin", "initials": "K"}, {"family": "Lindman", "given": "Kristina", "initials": "K"}, {"family": "Enquist", "given": "Per-Anders", "initials": "P"}, {"family": "Spjut", "given": "Sara", "initials": "S"}, {"family": "Allard", "given": "Annika", "initials": "A"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}, {"family": "Mei", "given": "Ya-Fang", "initials": "Y"}, {"family": "Wadell", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2010-09-00", "journal": {"volume": "54", "issn": "1098-6596", "issue": "9", "pages": "3871-3877", "title": "Antimicrob. Agents Chemother.", "issn-l": "0066-4804"}, "abstract": "Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their antiadenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential antiadenoviral compounds. The assay is unique in that it is based on a replication-competent adenovirus type 11p green fluorescent protein (GFP)-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by > or = 80%, but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.", "doi": "10.1128/AAC.00203-10", "pmid": "20585112", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AAC.00203-10"}, {"db": "pmc", "key": "PMC2935025"}], "notes": "Laboratories for Chemical Biology Ume\u00e5 (LCBU)", "created": "2017-05-04T14:56:36.118Z", "modified": "2025-10-17T13:04:30.833Z"}], "created": "2017-05-09T09:12:24.913Z", "modified": "2020-11-27T13:14:01.421Z"}