{"entity": "researcher", "timestamp": "2026-07-17T08:47:09.453Z", "family": "Andersson", "given": "Dan I", "initials": "DI", "orcid": "0000-0001-6640-2174", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/fb042b3dfa21450e862a29951ea0c1eb.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/fb042b3dfa21450e862a29951ea0c1eb"}}, "publications": [{"entity": "publication", "iuid": "d086ca68d3ff42dc9c2f5eaa0834b478", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d086ca68d3ff42dc9c2f5eaa0834b478.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d086ca68d3ff42dc9c2f5eaa0834b478"}}, "title": "Droplet microfluidics-based detection of rare antibiotic-resistant subpopulations in Escherichia coli from bloodstream infections.", "authors": [{"family": "Agnihotri", "given": "Sagar N", "initials": "SN", "orcid": "0000-0003-0943-6751", "researcher": {"href": "https://publications.scilifelab.se/researcher/c42c1834bf5247a38d98b8bab8b4914d.json"}}, {"family": "Fatsis-Kavalopoulos", "given": "Nikos", "initials": "N", "orcid": "0000-0002-5081-0138", "researcher": {"href": "https://publications.scilifelab.se/researcher/c173faa59bde4b908da82e02a23d4b70.json"}}, {"family": "Windhager", "given": "Jonas", "initials": "J", "orcid": "0000-0002-2111-5291", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbdf2ef632c740cdaba02c8ee61f2b62.json"}}, {"family": "Tenje", "given": "Maria", "initials": "M", "orcid": "0000-0002-1264-1337", "researcher": {"href": "https://publications.scilifelab.se/researcher/18affd576ee84f62a7a40f678a600058.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": "2025-07-04", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "27", "pages": "eadv4558", "issn-l": "2375-2548"}, "abstract": "Population heterogeneity in bacterial phenotypes, such as antibiotic resistance, is increasingly recognized as a medical concern. Heteroresistance occurs when a predominantly susceptible bacterial population harbors a rare resistant subpopulation. During antibiotic exposure, these resistant bacteria can be selected and lead to treatment failure. Standard antibiotic susceptibility testing methods often fail to reliably detect these subpopulations due to their low frequency, highlighting the need for improved diagnostic approaches. Here, we present a droplet microfluidics method where bacteria are encapsulated in droplets containing growth medium and antibiotics. The growth of rare resistant cells is detected by observing droplet shrinkage under microscopy. We validated this method for three clinically important antibiotics in Escherichia coli isolates obtained from bloodstream infections and showed that it can detect resistant subpopulations as infrequent as 10-6 using only 200 to 300 droplets. In addition, we designed a multiplex microfluidic chip to increase the throughput of the assay.", "doi": "10.1126/sciadv.adv4558", "pmid": "40614180", "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12227044"}], "notes": [], "created": "2025-11-25T12:57:58.095Z", "modified": "2025-11-25T12:57:58.278Z"}, {"entity": "publication", "iuid": "fd4b4d71ebb544eba77fab8cedca6a01", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fd4b4d71ebb544eba77fab8cedca6a01.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fd4b4d71ebb544eba77fab8cedca6a01"}}, "title": "Suppression of the Escherichia coli rnpA49 conditionally lethal phenotype by different compensatory mutations.", "authors": [{"family": "Babina", "given": "Arianne M", "initials": "AM", "orcid": "0000-0002-4635-8396", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbe7f6d7d7a64bc3b829bea72dc1ca63.json"}}, {"family": "Kirsebom", "given": "Leif A", "initials": "LA", "orcid": "0000-0002-5092-512X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e80849a89d0043b0b4daff9804c67332.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": "2024-07-16", "journal": {"title": "RNA", "issn": "1469-9001", "volume": "30", "issue": "8", "pages": "977-991", "issn-l": "1355-8382"}, "abstract": "RNase P is an essential enzyme found across all domains of life that is responsible for the 5'-end maturation of precursor tRNAs. For decades, numerous studies have sought to elucidate the mechanisms and biochemistry governing RNase P function. However, much remains unknown about the regulation of RNase P expression, the turnover and degradation of the enzyme, and the mechanisms underlying the phenotypes and complementation of specific RNase P mutations, especially in the model bacterium, Escherichia coli In E. coli, the temperature-sensitive (ts) rnpA49 mutation in the protein subunit of RNase P has arguably been one of the most well-studied mutations for examining the enzyme's activity in vivo. Here, we report for the first time naturally occurring temperature-resistant suppressor mutations of E. coli strains carrying the rnpA49 allele. We find that rnpA49 strains can partially compensate the ts defect via gene amplifications of either RNase P subunit (rnpA49 or rnpB) or by the acquisition of loss-of-function mutations in Lon protease or RNase R. Our results agree with previous plasmid overexpression and gene deletion complementation studies, and importantly suggest the involvement of Lon protease in the degradation and/or regulatory pathway(s) of the mutant protein subunit of RNase P. This work offers novel insights into the behavior and complementation of the rnpA49 allele in vivo and provides direction for follow-up studies regarding RNase P regulation and turnover in E. coli.", "doi": "10.1261/rna.079909.123", "pmid": "38688559", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11251521"}, {"db": "pii", "key": "rna.079909.123"}, {"db": "medline", "key": "9509184"}], "notes": [], "created": "2024-11-27T15:36:05.495Z", "modified": "2024-11-27T15:36:59.692Z"}, {"entity": "publication", "iuid": "43b7b34634d5450394e7d5bcbd769ef2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/43b7b34634d5450394e7d5bcbd769ef2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/43b7b34634d5450394e7d5bcbd769ef2"}}, "title": "Staphylococcus aureus mutants resistant to the feed-additive monensin show increased virulence and altered purine metabolism.", "authors": [{"family": "Warsi", "given": "Omar M", "initials": "OM", "orcid": "0000-0003-3175-1184", "researcher": {"href": "https://publications.scilifelab.se/researcher/719c086777ef4fd38d737c8254d612d8.json"}}, {"family": "Upterworth", "given": "Lina M", "initials": "LM"}, {"family": "Breidenstein", "given": "Annika", "initials": "A"}, {"family": "Lustig", "given": "Ulrika", "initials": "U"}, {"family": "Mikkelsen", "given": "Kasper", "initials": "K"}, {"family": "Nagy", "given": "Tam\u00e1s", "initials": "T"}, {"family": "Szatmari", "given": "D\u00e1vid", "initials": "D"}, {"family": "Ingmer", "given": "Hanne", "initials": "H", "orcid": "0000-0002-8350-5631", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ccbc7d775a6405bbd151375fc4ea5f2.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": "2024-02-14", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "15", "issue": "2", "pages": "e0315523", "issn-l": null}, "abstract": "Ionophores are antibacterial compounds that affect bacterial growth by changing intracellular concentrations of the essential cations, sodium and potassium. They are extensively used in animal husbandry to increase productivity and reduce infectious diseases, but our understanding of the potential for and effects of resistance development to ionophores is poorly known. Thus, given their widespread global usage, it is important to determine the potential negative consequences of ionophore use on human and animal health. In this study, we demonstrate that exposure to the ionophore monensin can select for resistant mutants in the human and animal pathogen Staphylococcus aureus, with a majority of the resistant mutants showing increased growth rates in vitro and/or in mice. Whole-genome sequencing and proteomic analysis of the resistant mutants show that the resistance phenotype is associated with de-repression of de novo purine synthesis, which could be achieved through mutations in different transcriptional regulators including mutations in the gene purR, the repressor of the purine de novo synthesis pathway. This study shows that mutants with reduced susceptibility to the ionophore monensin can be readily selected and highlights an unexplored link between ionophore resistance, purine metabolism, and fitness in pathogenic bacteria.IMPORTANCEThis study demonstrates a novel link between ionophore resistance, purine metabolism, and virulence/fitness in the key human and animal pathogen Staphylococcus aureus. The results show that mutants with reduced susceptibility to the commonly used ionophore monensin can be readily selected and that the reduced susceptibility observed is associated with an increased expression of the de novo purine synthesis pathway. This study increases our understanding of the impact of the use of animal feed additives on both human and veterinary medicine.", "doi": "10.1128/mbio.03155-23", "pmid": "38214510", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10865815"}], "notes": [], "created": "2024-11-27T15:37:02.138Z", "modified": "2025-11-20T18:17:58.115Z"}, {"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": "8d9a5bdc18694364a23ff3b134f7e069", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d9a5bdc18694364a23ff3b134f7e069.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d9a5bdc18694364a23ff3b134f7e069"}}, "title": "Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin.", "authors": [{"family": "Roemhild", "given": "Roderich", "initials": "R", "orcid": "0000-0001-9480-5261", "researcher": {"href": "https://publications.scilifelab.se/researcher/817ce0f8274f4a8d88867af5b4dad172.json"}}, {"family": "Linkevicius", "given": "Marius", "initials": "M", "orcid": "0000-0001-5760-2721", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3ef4e2dd7fa44bb91db1d4a5b855d72.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": "2020-01-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "volume": "18", "issue": "1", "pages": "e3000612", "issn-l": "1544-9173"}, "abstract": "Antibiotic resistance increasingly limits the success of antibiotic treatments, and physicians require new ways to achieve efficient treatment despite resistance. Resistance mechanisms against a specific antibiotic class frequently confer increased susceptibility to other antibiotic classes, a phenomenon designated collateral sensitivity (CS). An informed switch of antibiotic may thus enable the efficient treatment of resistant strains. CS occurs in many pathogens, but the mechanisms that generate hypersusceptibility are largely unknown. We identified several molecular mechanisms of CS against the antibiotic nitrofurantoin (NIT). Mutants that are resistant against tigecycline (tetracycline), mecillinam (\u03b2-lactam), and protamine (antimicrobial peptide) all show CS against NIT. Their hypersusceptibility is explained by the overexpression of nitroreductase enzymes combined with increased drug uptake rates, or increased drug toxicity. Increased toxicity occurs through interference of the native drug-response system for NIT, the SOS response, with growth. A mechanistic understanding of CS will help to develop drug switches that combat resistance.", "doi": "10.1371/journal.pbio.3000612", "pmid": "31986134", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "PBIOLOGY-D-19-02723"}, {"db": "pmc", "key": "PMC7004380"}], "notes": [], "created": "2020-01-30T15:58:40.458Z", "modified": "2024-01-16T13:46:31.019Z"}]}