{"entity": "journal", "iuid": "09dbe024885740da8a43bd5c3a2ca775", "timestamp": "2026-08-15T13:20:16.573Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/PLoS%20Pathog..json"}, "display": {"href": "https://publications.scilifelab.se/journal/PLoS%20Pathog."}}, "title": "PLoS Pathog.", "issn": "1553-7374", "issn-l": "1553-7366", "publications_count": 16, "publications": [{"entity": "publication", "iuid": "12010dd55a294967a7bec8f110ff6836", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12010dd55a294967a7bec8f110ff6836.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12010dd55a294967a7bec8f110ff6836"}}, "title": "Direct and indirect pathways linking the Lon protease to motility behaviors in the pathogen Pseudomonas aeruginosa.", "authors": [{"family": "Kallazhi", "given": "Aswathy", "initials": "A"}, {"family": "Rahman", "given": "Anamika", "initials": "A"}, {"family": "R\u00f6mling", "given": "Ute", "initials": "U"}, {"family": "Jonas", "given": "Kristina", "initials": "K", "orcid": "0000-0002-1469-4424", "researcher": {"href": "https://publications.scilifelab.se/researcher/3351b638c7904141b4ae20dd41929e26.json"}}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "21", "issue": "6", "pages": "e1013288", "issn-l": "1553-7366"}, "abstract": "The ATP-dependent cytoplasmic protease Lon has critical functions in protein quality control and cellular regulation in organisms across the three domains of life. In the opportunistic pathogen Pseudomonas aeruginosa, lon loss-of-function mutants exhibit multiple phenotypic defects in motility, virulence, antibiotic tolerance and biofilm formation. However, only a couple of native substrate proteins of Lon are described in P. aeruginosa until now and most of the phenotypes associated with Lon remain unexplained. Here, we searched for novel Lon substrates in P. aeruginosa by analyzing proteome-wide changes in protein levels and stabilities following lon overexpression. Our search yielded a large number of putative Lon substrates with diverse cellular functions, including metabolic enzymes, stress proteins and a significant fraction of motility-related proteins. In vitro degradation assays confirmed the metabolic protein SpeH, the heat shock protein IbpA as well as seven proteins involved in flagella- and type IV pilus-mediated motility as novel substrates of Lon. The new motility-associated substrates include both key regulators of motility (FliA, RpoN, AmrZ) as well as structural flagellar components (FliG, FliS and FlgE). Further, by isolating suppressor mutations bypassing the motility defect of lon- cells, we reveal that Lon-dependent degradation of the specific substrate SulA, a cell division inhibitor, is crucial for ensuring proper cell division and motility under optimal conditions. In sum, our work highlights Lon's regulatory role in degrading functional proteins involved in critical cellular processes and contributes to a better molecular understanding of the pathways underlying Pseudomonas pathogenicity.", "doi": "10.1371/journal.ppat.1013288", "pmid": "40561152", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12221181"}, {"db": "pii", "key": "PPATHOGENS-D-25-00035"}], "notes": [], "created": "2025-11-27T13:03:21.073Z", "modified": "2025-11-27T13:03:21.261Z"}, {"entity": "publication", "iuid": "2967b3adfd284d258eb3e53e7ee08740", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2967b3adfd284d258eb3e53e7ee08740.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2967b3adfd284d258eb3e53e7ee08740"}}, "title": "Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection.", "authors": [{"family": "Franz\u00e9n Boger", "given": "Mathias", "initials": "M", "orcid": "0009-0009-0219-3655", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2c4570f120843e5accc52936750547f.json"}}, {"family": "Hasselrot", "given": "Tyra", "initials": "T"}, {"family": "Kaldhusdal", "given": "Vilde", "initials": "V"}, {"family": "Miranda", "given": "Gisele H B", "initials": "GHB"}, {"family": "Czarnewski", "given": "Paulo", "initials": "P"}, {"family": "Edfeldt", "given": "Gabriella", "initials": "G"}, {"family": "Bradley", "given": "Frideborg", "initials": "F"}, {"family": "Rexaj", "given": "Genta", "initials": "G"}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "Omollo", "given": "Kenneth", "initials": "K"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Fowke", "given": "Keith R", "initials": "KR"}, {"family": "Broliden", "given": "Kristina", "initials": "K"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}], "type": "journal article", "published": "2024-11-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "issn-l": "1553-7366", "volume": "20", "issue": "11", "pages": "e1012709"}, "abstract": "Chronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Similarly, the consequences of chronic HIV infection on the integrity of the female genital epithelium are poorly understood, despite its importance in HIV transmission and replication. Ectocervical biopsies were obtained from HIV-seropositive (n = 14) and HIV-seronegative (n = 47) female Kenyan sex workers. RNA sequencing and bioimage analysis of epithelial junction proteins (E-cadherin, desmoglein-1, claudin-1, and zonula occludens-1) were conducted, along with CD4 staining. RNA sequencing revealed upregulation of immunoregulatory genes in HIV-seropositive women, primarily associated with heightened T cell activity and interferon signaling, which further correlated with plasma viral load. Transcription factor analysis confirmed the upregulation of pro-inflammatory transcription factors, such as RELA, NFKB1, and IKZF3, which facilitates HIV persistence in T cells. Conversely, genes and pathways associated with epithelial barrier function and structure were downregulated in the context of HIV. Digital bioimage analysis corroborated these findings, revealing significant disruption of various epithelial junction proteins in ectocervical tissues of the HIV-seropositive women. Thus, chronic HIV infection associated with ectocervical inflammation, characterized by induced T cell responses and interferon signaling, coupled with epithelial disruption. These alterations may influence HIV transmission and heighten susceptibility to other sexually transmitted infections. These findings prompt exploration of therapeutic interventions to address HIV-related complications and mitigate the risk of sexually transmitted infection transmission.", "doi": "10.1371/journal.ppat.1012709", "pmid": "39561211", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11614238"}, {"db": "pii", "key": "PPATHOGENS-D-24-01053"}], "notes": [], "created": "2025-01-23T12:50:40.544Z", "modified": "2025-11-19T08:52:45.412Z"}, {"entity": "publication", "iuid": "ef2d3d5294b7468cb8ee8edc0deb2226", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef2d3d5294b7468cb8ee8edc0deb2226.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef2d3d5294b7468cb8ee8edc0deb2226"}}, "title": "In vitro reconstitution reveals membrane clustering and RNA recruitment by the enteroviral AAA+ ATPase 2C.", "authors": [{"family": "Shankar", "given": "Kasturika", "initials": "K"}, {"family": "Sorin", "given": "Marie N", "initials": "MN"}, {"family": "Sharma", "given": "Himanshu", "initials": "H"}, {"family": "Skoglund", "given": "Oskar", "initials": "O"}, {"family": "Dahmane", "given": "Selma", "initials": "S"}, {"family": "Ter Beek", "given": "Josy", "initials": "J"}, {"family": "Tesfalidet", "given": "Solomon", "initials": "S"}, {"family": "Nenz\u00e9n", "given": "Louise", "initials": "L"}, {"family": "Carlson", "given": "Lars-Anders", "initials": "LA", "orcid": "0000-0003-2342-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba0e366ce21e49b48212bbed5a0a7bd1.json"}}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "20", "issue": "8", "pages": "e1012388", "issn-l": "1553-7366"}, "abstract": "Enteroviruses are a vast genus of positive-sense RNA viruses that cause diseases ranging from common cold to poliomyelitis and viral myocarditis. They encode a membrane-bound AAA+ ATPase, 2C, that has been suggested to serve several roles in virus replication, e.g. as an RNA helicase and capsid assembly factor. Here, we report the reconstitution of full-length, poliovirus 2C's association with membranes. We show that the N-terminal membrane-binding domain of 2C contains a conserved glycine, which is suggested by structure predictions to divide the domain into two amphipathic helix regions, which we name AH1 and AH2. AH2 is the main mediator of 2C oligomerization, and is necessary and sufficient for its membrane binding. AH1 is the main mediator of a novel function of 2C: clustering of membranes. Cryo-electron tomography reveal that several 2C copies mediate this function by localizing to vesicle-vesicle interfaces. 2C-mediated clustering is partially outcompeted by RNA, suggesting a way by which 2C can switch from an early role in coalescing replication organelles and lipid droplets, to a later role where 2C assists RNA replication and particle assembly. 2C is sufficient to recruit RNA to membranes, with a preference for double-stranded RNA (the replicating form of the viral genome). Finally, the in vitro reconstitution revealed that full-length, membrane-bound 2C has ATPase activity and ATP-independent, single-strand ribonuclease activity, but no detectable helicase activity. Together, this study suggests novel roles for 2C in membrane clustering, RNA membrane recruitment and cleavage, and calls into question a role of 2C as an RNA helicase. The reconstitution of functional, 2C-decorated vesicles provides a platform for further biochemical studies into this protein and its roles in enterovirus replication.", "doi": "10.1371/journal.ppat.1012388", "pmid": "39102425", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11326647"}, {"db": "pii", "key": "PPATHOGENS-D-24-01299"}], "notes": [], "created": "2024-11-27T11:35:52.560Z", "modified": "2025-10-29T14:48:32.645Z"}, {"entity": "publication", "iuid": "c15fafc80ac34f6d886e21e59ba35e01", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c15fafc80ac34f6d886e21e59ba35e01.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c15fafc80ac34f6d886e21e59ba35e01"}}, "title": "High-resolution comparative atomic structures of two Giardiavirus prototypes infecting G. duodenalis parasite.", "authors": [{"family": "Wang", "given": "Han", "initials": "H", "orcid": "0000-0002-6445-2095", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a6c888a8fa948a496030381158af8fb.json"}}, {"family": "Marucci", "given": "Gianluca", "initials": "G"}, {"family": "Munke", "given": "Anna", "initials": "A", "orcid": "0000-0002-5510-2245", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd6d8030171420190aa65f3eb1ac4bd.json"}}, {"family": "Hassan", "given": "Mohammad Maruf", "initials": "MM"}, {"family": "Lalle", "given": "Marco", "initials": "M", "orcid": "0000-0001-5168-2150", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a28b6fb80c746d792742cf2fa282302.json"}}, {"family": "Okamoto", "given": "Kenta", "initials": "K", "orcid": "0000-0002-4858-1196", "researcher": {"href": "https://publications.scilifelab.se/researcher/9302e76f16a04afdbb72f00c805bffa4.json"}}], "type": "journal article", "published": "2024-04-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "20", "issue": "4", "pages": "e1012140", "issn-l": "1553-7366"}, "abstract": "The Giardia lamblia virus (GLV) is a non-enveloped icosahedral dsRNA and endosymbiont virus that infects the zoonotic protozoan parasite Giardia duodenalis (syn. G. lamblia, G. intestinalis), which is a pathogen of mammals, including humans. Elucidating the transmission mechanism of GLV is crucial for gaining an in-depth understanding of the virulence of the virus in G. duodenalis. GLV belongs to the family Totiviridae, which infects yeast and protozoa intracellularly; however, it also transmits extracellularly, similar to the phylogenetically, distantly related toti-like viruses that infect multicellular hosts. The GLV capsid structure is extensively involved in the longstanding discussion concerning extracellular transmission in Totiviridae and toti-like viruses. Hence, this study constructed the first high-resolution comparative atomic models of two GLV strains, namely GLV-HP and GLV-CAT, which showed different intracellular localization and virulence phenotypes, using cryogenic electron microscopy single-particle analysis. The atomic models of the GLV capsids presented swapped C-terminal extensions, extra surface loops, and a lack of cap-snatching pockets, similar to those of toti-like viruses. However, their open pores and absence of the extra crown protein resemble those of other yeast and protozoan Totiviridae viruses, demonstrating the essential structures for extracellular cell-to-cell transmission. The structural comparison between GLV-HP and GLV-CAT indicates the first evidence of critical structural motifs for the transmission and virulence of GLV in G. duodenalis.", "doi": "10.1371/journal.ppat.1012140", "pmid": "38598600", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11081498"}, {"db": "pii", "key": "PPATHOGENS-D-23-01960"}], "notes": [], "created": "2025-01-20T09:05:08.219Z", "modified": "2025-11-13T10:43:18.700Z"}, {"entity": "publication", "iuid": "63814c2828f14ee58cef696374d723d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/63814c2828f14ee58cef696374d723d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/63814c2828f14ee58cef696374d723d9"}}, "title": "Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection.", "authors": [{"family": "Gr\u00fcttner", "given": "Jana", "initials": "J", "orcid": "0000-0002-2507-3375", "researcher": {"href": "https://publications.scilifelab.se/researcher/28fb027f36d94b85afb5e1325fd0ed7b.json"}}, {"family": "van Rijn", "given": "Jorik M", "initials": "JM", "orcid": "0000-0003-2865-4455", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f2defce179d4632a4e7d60666417ab2.json"}}, {"family": "Geiser", "given": "Petra", "initials": "P", "orcid": "0000-0003-2785-4201", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae0bf10f41dc4698b19288809bae2dd6.json"}}, {"family": "Florbrant", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-1630-4442", "researcher": {"href": "https://publications.scilifelab.se/researcher/360f8004f9394dabb68f1f9e0725e42c.json"}}, {"family": "Webb", "given": "Dominic-Luc", "initials": "DL", "orcid": "0000-0002-6979-9194", "researcher": {"href": "https://publications.scilifelab.se/researcher/868fca24b48f440eb2417acdb04e73d3.json"}}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM", "orcid": "0000-0001-8428-0772", "researcher": {"href": "https://publications.scilifelab.se/researcher/e85863b505f34d7e95a23ac127b9d6dc.json"}}, {"family": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications.scilifelab.se/researcher/a54316faa45947bd92615d27a38c2b87.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications.scilifelab.se/researcher/f797357bcd3d4447bff96c20873dd500.json"}}, {"family": "Sv\u00e4rd", "given": "Staffan G", "initials": "SG", "orcid": "0000-0002-7392-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/b01942d70ef84a1db3aaccab65af9c57.json"}}], "type": "journal article", "published": "2023-05-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "19", "issue": "5", "pages": "e1011372", "issn-l": "1553-7366"}, "abstract": "Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, \"non-fit\" or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, \"fit\" trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.", "doi": "10.1371/journal.ppat.1011372", "pmid": "37141303", "labels": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10187934"}, {"db": "pii", "key": "PPATHOGENS-D-22-02213"}], "notes": [], "created": "2023-05-22T07:22:26.525Z", "modified": "2023-05-22T07:22:26.821Z"}, {"entity": "publication", "iuid": "2ed2f8fb4b724d8691db59fd2b49f172", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2ed2f8fb4b724d8691db59fd2b49f172.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2ed2f8fb4b724d8691db59fd2b49f172"}}, "title": "Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein.", "authors": [{"family": "Pulkkinen", "given": "Lauri Ilmari Aurelius", "initials": "LIA"}, {"family": "Barrass", "given": "Sarah Victoria", "initials": "SV"}, {"family": "Lindgren", "given": "Marie", "initials": "M"}, {"family": "Pace", "given": "Hudson", "initials": "H"}, {"family": "\u00d6verby", "given": "Anna K", "initials": "AK"}, {"family": "Anastasina", "given": "Maria", "initials": "M"}, {"family": "Bally", "given": "Marta", "initials": "M"}, {"family": "Lundmark", "given": "Richard", "initials": "R"}, {"family": "Butcher", "given": "Sarah Jane", "initials": "SJ", "orcid": "0000-0001-7060-5871", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7076e70172b45d7ab9de4ab86775ae9.json"}}], "type": "journal article", "published": "2023-02-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "19", "issue": "2", "pages": "e1011125", "issn-l": "1553-7366"}, "abstract": "Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate the interactions of the wild-type and truncated capsid proteins with membranes with biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids, which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.", "doi": "10.1371/journal.ppat.1011125", "pmid": "36787339", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9970071"}, {"db": "pii", "key": "PPATHOGENS-D-23-00047"}], "notes": [], "created": "2023-08-30T07:08:43.930Z", "modified": "2025-10-17T13:03:14.356Z"}, {"entity": "publication", "iuid": "8f5c4ba7fc9d49f7a95e4de38aaee0f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8f5c4ba7fc9d49f7a95e4de38aaee0f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8f5c4ba7fc9d49f7a95e4de38aaee0f4"}}, "title": "Evolution, geographic spreading, and demographic distribution of Enterovirus D68.", "authors": [{"family": "Hodcroft", "given": "Emma B", "initials": "EB", "orcid": "0000-0002-0078-2212", "researcher": {"href": "https://publications.scilifelab.se/researcher/fdecbfc127f54d2f8a15f5b8ff29a63e.json"}}, {"family": "Dyrdak", "given": "Robert", "initials": "R", "orcid": "0000-0001-8456-4898", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b0e7b74466d4b1688a654479f99f0d9.json"}}, {"family": "Andr\u00e9s", "given": "Cristina", "initials": "C", "orcid": "0000-0002-3200-0895", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8bd70da8194ad29fd70fe885d218da.json"}}, {"family": "Egli", "given": "Adrian", "initials": "A"}, {"family": "Reist", "given": "Josiane", "initials": "J"}, {"family": "Garc\u00eda Mart\u00ednez de Artola", "given": "Diego", "initials": "D", "orcid": "0000-0003-0771-5968", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d13a651ee264d1194d59f0544adf07a.json"}}, {"family": "Alcoba-Fl\u00f3rez", "given": "Julia", "initials": "J", "orcid": "0000-0002-7778-3248", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4fdc6b3e8f54152b681f8a1a91db1f5.json"}}, {"family": "Niesters", "given": "Hubert G M", "initials": "HGM", "orcid": "0000-0002-1758-0430", "researcher": {"href": "https://publications.scilifelab.se/researcher/d08fde4270e944ceb8c0559b53e0396b.json"}}, {"family": "Ant\u00f3n", "given": "Andr\u00e9s", "initials": "A", "orcid": "0000-0002-1476-0815", "researcher": {"href": "https://publications.scilifelab.se/researcher/29c667ca53dd40df853d89554e6d7d04.json"}}, {"family": "Poelman", "given": "Randy", "initials": "R"}, {"family": "Reynders", "given": "Marijke", "initials": "M", "orcid": "0000-0003-2079-1279", "researcher": {"href": "https://publications.scilifelab.se/researcher/447a8e971cdf42bbb32000364ec5c6c4.json"}}, {"family": "Wollants", "given": "Elke", "initials": "E", "orcid": "0000-0002-4057-2236", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1ef51019ff24427b8267143a1f14c5e.json"}}, {"family": "Neher", "given": "Richard A", "initials": "RA", "orcid": "0000-0003-2525-1407", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0e01851bb1f489a949de83bb043f56c.json"}}, {"family": "Albert", "given": "Jan", "initials": "J", "orcid": "0000-0001-9020-0521", "researcher": {"href": "https://publications.scilifelab.se/researcher/d23f55d392eb411d90a53c2fb22aced3.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "18", "issue": "5", "pages": "e1010515", "issn-l": "1553-7366"}, "abstract": "Worldwide outbreaks of enterovirus D68 (EV-D68) in 2014 and 2016 have caused serious respiratory and neurological disease. We collected samples from several European countries during the 2018 outbreak and determined 53 near full-length genome ('whole genome') sequences. These sequences were combined with 718 whole genome and 1,987 VP1-gene publicly available sequences. In 2018, circulating strains clustered into multiple subgroups in the B3 and A2 subclades, with different phylogenetic origins. Clusters in subclade B3 emerged from strains circulating primarily in the US and Europe in 2016, though some had deeper roots linking to Asian strains, while clusters in A2 traced back to strains detected in East Asia in 2015-2016. In 2018, all sequences from the USA formed a distinct subgroup, containing only three non-US samples. Alongside the varied origins of seasonal strains, we found that diversification of these variants begins up to 18 months prior to the first diagnostic detection during a EV-D68 season. EV-D68 displays strong signs of continuous antigenic evolution and all 2018 A2 strains had novel patterns in the putative neutralizing epitopes in the BC- and DE-loops. The pattern in the BC-loop of the USA B3 subgroup had not been detected on that continent before. Patients with EV-D68 in subclade A2 were significantly older than patients with a B3 subclade virus. In contrast to other subclades, the age distribution of A2 is distinctly bimodal and was found primarily among children and in the elderly. We hypothesize that EV-D68's rapid evolution of surface proteins, extensive diversity, and high rate of geographic mixing could be explained by substantial reinfection of adults. Better understanding of evolution and immunity across diverse viral pathogens, including EV-D68 and SARS-CoV-2, is critical to pandemic preparedness in the future.", "doi": "10.1371/journal.ppat.1010515", "pmid": "35639811", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9212145"}, {"db": "pii", "key": "PPATHOGENS-D-21-02040"}], "notes": [], "created": "2022-11-27T21:35:18.283Z", "modified": "2022-11-27T21:35:18.734Z"}, {"entity": "publication", "iuid": "a0a0ece375d24f3fafa2a00b725911ff", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0a0ece375d24f3fafa2a00b725911ff.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0a0ece375d24f3fafa2a00b725911ff"}}, "title": "Multi-omics analysis of the cervical epithelial integrity of women using depot medroxyprogesterone acetate.", "authors": [{"family": "Bradley", "given": "Frideborg", "initials": "F", "orcid": "0000-0003-3006-7284", "researcher": {"href": "https://publications.scilifelab.se/researcher/d51eaeb949e94bd39ab3605d495dc647.json"}}, {"family": "Franz\u00e9n Boger", "given": "Mathias", "initials": "M"}, {"family": "Kaldhusdal", "given": "Vilde", "initials": "V"}, {"family": "\u00c5hlberg", "given": "Alexandra", "initials": "A"}, {"family": "Edfeldt", "given": "Gabriella", "initials": "G"}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "Bergstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Omollo", "given": "Kenneth", "initials": "K"}, {"family": "Damdimopoulos", "given": "Anastasios", "initials": "A"}, {"family": "Czarnewski", "given": "Paulo", "initials": "P"}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A"}, {"family": "Oyugi", "given": "Julius", "initials": "J"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Nilsson", "given": "Peter", "initials": "P"}, {"family": "Fowke", "given": "Keith", "initials": "K"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}, {"family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "18", "issue": "5", "pages": "e1010494", "issn-l": "1553-7366"}, "abstract": "Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n = 32) or regularly cycling controls (n = 64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4+ cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.", "doi": "10.1371/journal.ppat.1010494", "pmid": "35533147", "labels": {"BioImage Informatics": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9119532"}, {"db": "pii", "key": "PPATHOGENS-D-21-02612"}], "notes": [], "created": "2022-08-30T13:46:44.982Z", "modified": "2022-12-07T11:49:48.217Z"}, {"entity": "publication", "iuid": "f8cca6c2565442529e2d305f9df9d713", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8cca6c2565442529e2d305f9df9d713.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8cca6c2565442529e2d305f9df9d713"}}, "title": "Defining the proteolytic landscape during enterovirus infection.", "authors": [{"family": "Saeed", "given": "Mohsan", "initials": "M", "orcid": "0000-0001-8505-7054", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2b550e450e648b88973f7806e69d9e0.json"}}, {"family": "Kapell", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-9304-558X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cffd944f88e54ed6a910183ba49ef656.json"}}, {"family": "Hertz", "given": "Nicholas T", "initials": "NT", "orcid": "0000-0002-6527-6898", "researcher": {"href": "https://publications.scilifelab.se/researcher/3718edc733f9468b8bc3986691d78d11.json"}}, {"family": "Wu", "given": "Xianfang", "initials": "X"}, {"family": "Bell", "given": "Kierstin", "initials": "K"}, {"family": "Ashbrook", "given": "Alison W", "initials": "AW", "orcid": "0000-0003-1114-1426", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c44306c97f44ea9af73e91263c7fca0.json"}}, {"family": "Mark", "given": "Milica Tesic", "initials": "MT"}, {"family": "Zebroski", "given": "Henry A", "initials": "HA", "orcid": "0000-0003-3012-2335", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d1648b613134dcb940eed28dd8ada81.json"}}, {"family": "Neal", "given": "Maxwell L", "initials": "ML", "orcid": "0000-0002-2390-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/c26ff0117fa24bc1b0eb24c0eeb99065.json"}}, {"family": "Flodstr\u00f6m-Tullberg", "given": "Malin", "initials": "M", "orcid": "0000-0003-2685-2052", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb6d04afbe8141c2b9297854de64dab8.json"}}, {"family": "MacDonald", "given": "Margaret R", "initials": "MR", "orcid": "0000-0001-5177-2068", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfa709cba63140a381f532f9d5379d7a.json"}}, {"family": "Aitchison", "given": "John D", "initials": "JD"}, {"family": "Molina", "given": "Henrik", "initials": "H"}, {"family": "Rice", "given": "Charles M", "initials": "CM", "orcid": "0000-0003-3087-8079", "researcher": {"href": "https://publications.scilifelab.se/researcher/34f03294e8e748779a10ecfcb1bf66b2.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "16", "issue": "9", "pages": "e1008927", "issn-l": "1553-7366"}, "abstract": "Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a p body protein with a role in antiviral immunity, showed that cleavage of this protein disrupts its antiviral function. This study yields a new depth of information about the host interface with a group of viruses that are both important biological tools and significant agents of disease.", "doi": "10.1371/journal.ppat.1008927", "pmid": "32997711", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7549765"}, {"db": "pii", "key": "PPATHOGENS-D-20-01061"}], "notes": [], "created": "2024-04-03T14:18:40.135Z", "modified": "2024-04-03T14:18:41.736Z"}, {"entity": "publication", "iuid": "bfb15759c8644cef8d58bca5a0c0e8c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bfb15759c8644cef8d58bca5a0c0e8c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bfb15759c8644cef8d58bca5a0c0e8c7"}}, "title": "MrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation.", "authors": [{"family": "Jiang", "given": "Wangshu", "initials": "W", "orcid": "0000-0003-1570-1208", "researcher": {"href": "https://publications.scilifelab.se/researcher/9908e45f950149e2963961d88783dabb.json"}}, {"family": "Ubhayasekera", "given": "Wimal", "initials": "W", "orcid": "0000-0001-5223-2434", "researcher": {"href": "https://publications.scilifelab.se/researcher/a01d8f6c38d3494a972b80f588f51f51.json"}}, {"family": "Breed", "given": "Michael C", "initials": "MC"}, {"family": "Norsworthy", "given": "Allison N", "initials": "AN"}, {"family": "Serr", "given": "Nina", "initials": "N", "orcid": "0000-0003-1335-0790", "researcher": {"href": "https://publications.scilifelab.se/researcher/5468ea52baea4e33a0c64ce395093c2d.json"}}, {"family": "Mobley", "given": "Harry L T", "initials": "HLT", "orcid": "0000-0001-9195-7665", "researcher": {"href": "https://publications.scilifelab.se/researcher/4db7193117fd4f5aaa3e2685372f01e2.json"}}, {"family": "Pearson", "given": "Melanie M", "initials": "MM", "orcid": "0000-0003-4553-3276", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c675562ba474fdb81810f9fec308fe6.json"}}, {"family": "Knight", "given": "Stefan D", "initials": "SD", "orcid": "0000-0002-7180-8758", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9971d1ebb542a8b54601675c3869f5.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "16", "issue": "8", "pages": "e1008707", "issn-l": "1553-7366"}, "abstract": "Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor.", "doi": "10.1371/journal.ppat.1008707", "pmid": "32780778", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7444556"}, {"db": "pii", "key": "PPATHOGENS-D-20-00342"}], "notes": [], "created": "2024-04-03T13:40:54.913Z", "modified": "2024-04-03T13:40:56.097Z"}, {"entity": "publication", "iuid": "822d35eda2b54d849cd9c0b5e61cf84c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/822d35eda2b54d849cd9c0b5e61cf84c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/822d35eda2b54d849cd9c0b5e61cf84c"}}, "title": "Nubbin isoform antagonism governs Drosophila intestinal immune homeostasis.", "authors": [{"family": "Lindberg", "given": "Bo G", "initials": "BG"}, {"family": "Tang", "given": "Xiongzhuo", "initials": "X"}, {"family": "Dantoft", "given": "Widad", "initials": "W"}, {"family": "Gohel", "given": "Priya", "initials": "P"}, {"family": "Seyedoleslami Esfahani", "given": "Shiva", "initials": "S"}, {"family": "Lindvall", "given": "Jessica M", "initials": "JM", "orcid": "0000-0002-5042-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/78debae1bc714b11a97ecf9e9656f1eb.json"}}, {"family": "Engstr\u00f6m", "given": "Ylva", "initials": "Y"}], "type": "journal article", "published": "2018-03-00", "journal": {"volume": "14", "issn": "1553-7374", "issue": "3", "pages": "e1006936", "title": "PLoS Pathog.", "issn-l": "1553-7366"}, "abstract": "Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub) encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila. Global transcriptional profiling of adult flies overexpressing Nub-PB in immunocompetent tissues revealed that this form is a strong transcriptional activator of a large set of immune genes. Further genetic analyses showed that Nub-PB is sufficient to drive expression both independently and in conjunction with nuclear factor kappa B (NF-\u03baB), JNK and JAK/STAT pathways. Similar overexpression of Nub-PD did, conversely, repress expression of the same targets. Strikingly, isoform co-overexpression normalized immune gene transcription, suggesting antagonistic activities. RNAi-mediated knockdown of individual nub transcripts in enterocytes confirmed antagonistic regulation by the two isoforms and that both are necessary for normal immune gene transcription in the midgut. Furthermore, enterocyte-specific Nub-PB expression levels had a strong impact on gut bacterial load as well as host lifespan. Overexpression of Nub-PB enhanced bacterial clearance of ingested Erwinia carotovora carotovora 15. Nevertheless, flies quickly succumbed to the infection, suggesting a deleterious immune response. In line with this, prolonged overexpression promoted a proinflammatory signature in the gut with induction of JNK and JAK/STAT pathways, increased apoptosis and stem cell proliferation. These findings highlight a novel regulatory mechanism of host-microbe interactions mediated by antagonistic transcription factor isoforms.", "doi": "10.1371/journal.ppat.1006936", "pmid": "29499056", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PPATHOGENS-D-17-02350"}, {"db": "pmc", "key": "PMC5851638"}], "notes": [], "created": "2019-01-15T07:55:56.735Z", "modified": "2021-07-05T12:48:16.004Z"}, {"entity": "publication", "iuid": "1240bd4e98cc469885a81a0e403b351f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1240bd4e98cc469885a81a0e403b351f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1240bd4e98cc469885a81a0e403b351f"}}, "title": "Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome.", "authors": [{"family": "Gupta", "given": "Soham", "initials": "S"}, {"family": "Yl\u00e4-Anttila", "given": "P\u00e4ivi", "initials": "P", "orcid": "0000-0002-5794-5094", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6e39574c18b4bb2a7aeb615ec0390bf.json"}}, {"family": "Callegari", "given": "Simone", "initials": "S"}, {"family": "Tsai", "given": "Ming-Han", "initials": "MH", "orcid": "0000-0001-5563-3057", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a910bb9a19c4ea18aa27eaec813ac72.json"}}, {"family": "Delecluse", "given": "Henri-Jacques", "initials": "HJ"}, {"family": "Masucci", "given": "Maria G", "initials": "MG", "orcid": "0000-0002-5541-2809", "researcher": {"href": "https://publications.scilifelab.se/researcher/7587ecb1b6a04380b54bd3be6b118d8a.json"}}], "type": "journal article", "published": "2018-01-00", "journal": {"volume": "14", "issn": "1553-7374", "issue": "1", "pages": "e1006852", "title": "PLoS Pathog.", "issn-l": "1553-7366"}, "abstract": "The N-terminal domains of the herpesvirus large tegument proteins encode a conserved cysteine protease with ubiquitin- and NEDD8-specific deconjugase activity. The proteins are expressed during the productive virus cycle and are incorporated into infectious virus particles, being delivered to the target cells upon primary infection. Members of this viral enzyme family were shown to regulate different aspects of the virus life cycle and the innate anti-viral response. However, only few substrates have been identified and the mechanisms of these effects remain largely unknown. In order to gain insights on the substrates and signaling pathways targeted by the viral enzymes, we have used co-immunoprecipitation and mass spectrometry to identify cellular proteins that interact with the Epstein-Barr virus encoded homologue BPLF1. Several members of the 14-3-3-family of scaffold proteins were found amongst the top hits of the BPLF1 interactome, suggesting that, through this interaction, BPLF1 may regulate a variety of cellular signaling pathways. Analysis of the shared protein-interaction network revealed that BPLF1 promotes the assembly of a tri-molecular complex including, in addition to 14-3-3, the ubiquitin ligase TRIM25 that participates in the innate immune response via ubiquitination of cytosolic pattern recognition receptor, RIG-I. The involvement of BPLF1 in the regulation of this signaling pathway was confirmed by inhibition of the type-I IFN responses in cells transfected with a catalytically active BPLF1 N-terminal domain or expressing the endogenous protein upon reactivation of the productive virus cycle. We found that the active viral enzyme promotes the dimerization and autoubiquitination of TRIM25. Upon triggering of the IFN response, RIG-I is recruited to the complex but ubiquitination is severely impaired, which functionally inactivates the RIG-I signalosome. The capacity to bind to and functionally inactivate the RIG-I signalosome is shared by the homologues encoded by other human herpesviruses.", "doi": "10.1371/journal.ppat.1006852", "pmid": "29357390", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "PPATHOGENS-D-17-01636"}, {"db": "pmc", "key": "PMC5794190"}], "notes": [], "created": "2019-01-07T11:23:21.564Z", "modified": "2021-06-21T14:35:18.968Z"}, {"entity": "publication", "iuid": "982dd1cdc3434cd8b71078d29f9a0a97", "links": {"self": {"href": "https://publications.scilifelab.se/publication/982dd1cdc3434cd8b71078d29f9a0a97.json"}, "display": {"href": "https://publications.scilifelab.se/publication/982dd1cdc3434cd8b71078d29f9a0a97"}}, "title": "BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming.", "authors": [{"family": "Bollampalli", "given": "Vishnu Priya", "initials": "VP"}, {"family": "Harumi Yamashiro", "given": "L\u00edvia", "initials": "L"}, {"family": "Feng", "given": "Xiaogang", "initials": "X"}, {"family": "Bierschenk", "given": "Dami\u00ebn", "initials": "D"}, {"family": "Gao", "given": "Yu", "initials": "Y"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Henriques-Normark", "given": "Birgitta", "initials": "B"}, {"family": "Nyl\u00e9n", "given": "Susanne", "initials": "S"}, {"family": "Rothfuchs", "given": "Antonio Gigliotti", "initials": "AG"}], "type": "journal article", "published": "2015-10-00", "journal": {"volume": "11", "issn": "1553-7374", "issue": "10", "pages": "e1005206", "title": "PLoS Pathog.", "issn-l": "1553-7366"}, "abstract": "The transport of antigen from the periphery to the draining lymph node (DLN) is critical for T-cell priming but remains poorly studied during infection with Mycobacterium bovis Bacille Calmette-Gu\u00e9rin (BCG). To address this we employed a mouse model to track the traffic of Dendritic cells (DCs) and mycobacteria from the BCG inoculation site in the skin to the DLN. Detection of BCG in the DLN was concomitant with the priming of antigen-specific CD4+ T cells at that site. We found EpCAMlow CD11bhigh migratory skin DCs to be mobilized during the transport of BCG to the DLN. Migratory skin DCs distributed to the T-cell area of the LN, co-localized with BCG and were found in close apposition to antigen-specific CD4+ T cells. Consequently, blockade of skin DC traffic into DLN dramatically reduced mycobacterial entry into DLN and muted T-cell priming. Interestingly, DC and mycobacterial entry into the DLN was dependent on IL-1R-I, MyD88, TNFR-I and IL-12p40. In addition, we found using DC adoptive transfers that the requirement for MyD88 in BCG-triggered migration was not restricted to the migrating DC itself and that hematopoietic expression of MyD88 was needed in part for full-fledged migration. Our observations thus identify a population of DCs that contribute towards the priming of CD4+ T cells to BCG infection by transporting bacilli into the DLN in an IL-1R-MyD88-dependent manner and reveal both DC-intrinsic and -extrinsic requirements for MyD88 in DC migration.", "doi": "10.1371/journal.ppat.1005206", "pmid": "26440518", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "PPATHOGENS-D-15-00825"}, {"db": "pmc", "key": "PMC4594926"}], "notes": [], "created": "2017-05-02T12:58:49.992Z", "modified": "2021-07-05T13:48:51.573Z"}, {"entity": "publication", "iuid": "4ee5619e9ea64ca8bb344583509cefa6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4ee5619e9ea64ca8bb344583509cefa6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4ee5619e9ea64ca8bb344583509cefa6"}}, "title": "Reprogramming of Yersinia from virulent to persistent mode revealed by complex in vivo RNA-seq analysis.", "authors": [{"family": "Avican", "given": "Kemal", "initials": "K"}, {"family": "Fahlgren", "given": "Anna", "initials": "A"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Heroven", "given": "Ann Kathrin", "initials": "AK"}, {"family": "Beckstette", "given": "Michael", "initials": "M"}, {"family": "Dersch", "given": "Petra", "initials": "P"}, {"family": "F\u00e4llman", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2015-01-00", "journal": {"volume": "11", "issn": "1553-7374", "issue": "1", "pages": "e1004600", "title": "PLoS Pathog.", "issn-l": "1553-7366"}, "abstract": "We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.", "doi": "10.1371/journal.ppat.1004600", "pmid": "25590628", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PPATHOGENS-D-14-01532"}, {"db": "pmc", "key": "PMC4295882"}, {"db": "GEO", "key": "GSE56477"}], "notes": [], "created": "2017-05-02T12:56:32.545Z", "modified": "2020-01-21T13:53:21.171Z"}, {"entity": "publication", "iuid": "f368c76367db4f02886060683e16b0dc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f368c76367db4f02886060683e16b0dc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f368c76367db4f02886060683e16b0dc"}}, "title": "Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.", "authors": [{"family": "Bachmann", "given": "Julie", "initials": "J"}, {"family": "Burt\u00e9", "given": "Florence", "initials": "F"}, {"family": "Pramana", "given": "Setia", "initials": "S"}, {"family": "Conte", "given": "Ianina", "initials": "I"}, {"family": "Brown", "given": "Biobele J", "initials": "BJ"}, {"family": "Orimadegun", "given": "Adebola E", "initials": "AE"}, {"family": "Ajetunmobi", "given": "Wasiu A", "initials": "WA"}, {"family": "Afolabi", "given": "Nathaniel K", "initials": "NK"}, {"family": "Akinkunmi", "given": "Francis", "initials": "F"}, {"family": "Omokhodion", "given": "Samuel", "initials": "S"}, {"family": "Akinbami", "given": "Felix O", "initials": "FO"}, {"family": "Shokunbi", "given": "Wuraola A", "initials": "WA"}, {"family": "Kampf", "given": "Caroline", "initials": "C"}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Sodeinde", "given": "Olugbemiro", "initials": "O"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Wahlgren", "given": "Mats", "initials": "M"}, {"family": "Fernandez-Reyes", "given": "Delmiro", "initials": "D"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}], "type": "journal article", "published": "2014-04-00", "journal": {"volume": "10", "issn": "1553-7374", "issue": "4", "pages": "e1004038", "title": "PLoS Pathog.", "issn-l": "1553-7366"}, "abstract": "Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.", "doi": "10.1371/journal.ppat.1004038", "pmid": "24743550", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PPATHOGENS-D-13-01973"}, {"db": "pmc", "key": "PMC3990714"}], "notes": [], "created": "2017-05-04T14:55:40.729Z", "modified": "2021-07-08T13:44:33.732Z"}, {"entity": "publication", "iuid": "aab1bb0d345742de954ec55b4ff5f7f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aab1bb0d345742de954ec55b4ff5f7f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aab1bb0d345742de954ec55b4ff5f7f4"}}, "title": "The Pseudomonas aeruginosa N-acylhomoserine lactone quorum sensing molecules target IQGAP1 and modulate epithelial cell migration.", "authors": [{"family": "Karlsson", "given": "Thommie", "initials": "T"}, {"family": "Turkina", "given": "Maria V", "initials": "MV"}, {"family": "Yakymenko", "given": "Olena", "initials": "O"}, {"family": "Magnusson", "given": "Karl-Eric", "initials": "K"}, {"family": "Vikstr\u00f6m", "given": "Elena", "initials": "E"}], "type": "journal article", "published": "2012-10-11", "journal": {"volume": "8", "issn": "1553-7374", "issue": "10", "pages": "e1002953", "title": "PLoS Pathog.", "issn-l": "1553-7366"}, "abstract": "Quorum sensing (QS) signaling allows bacteria to control gene expression once a critical population density is achieved. The Gram-negative human pathogen Pseudomonas aeruginosa uses N-acylhomoserine lactones (AHL) as QS signals, which coordinate the production of virulence factors and biofilms. These bacterial signals can also modulate human cell behavior. Little is known about the mechanisms of the action of AHL on their eukaryotic targets. Here, we found that N-3-oxo-dodecanoyl-L-homoserine lactone 3O-C(12)-HSL modulates human intestinal epithelial Caco-2 cell migration in a dose- and time-dependent manner. Using new 3O-C(12)-HSL biotin and fluorescently-tagged probes for LC-MS/MS and confocal imaging, respectively, we demonstrated for the first time that 3O-C(12)-HSL interacts and co-localizes with the IQ-motif-containing GTPase-activating protein IQGAP1 in Caco-2 cells. The interaction between IQGAP1 and 3O-C(12)-HSL was further confirmed by pull-down assay using a GST-tagged protein with subsequent Western blot of IQGAP1 and by identifying 3O-C(12)-HSL with a sensor bioassay. Moreover, 3O-C(12)-HSL induced changes in the phosphorylation status of Rac1 and Cdc42 and the localization of IQGAP1 as evidenced by confocal and STED microscopy and Western blots. Our findings suggest that the IQGAP1 is a novel partner for P. aeruginosa 3O-C(12)-HSL and likely the integrator of Rac1 and Cdc42- dependent altered cell migration. We propose that the targeting of IQGAP1 by 3O-C(12)-HSL can trigger essential changes in the cytoskeleton network and be an essential component in bacterial--human cell communication.", "doi": "10.1371/journal.ppat.1002953", "pmid": "23071436", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "PPATHOGENS-D-11-02789"}, {"db": "pmc", "key": "PMC3469656"}], "notes": [], "created": "2017-05-04T14:56:11.216Z", "modified": "2021-05-24T15:33:38.317Z"}], "created": "2017-05-09T09:12:20.473Z", "modified": "2020-11-27T13:14:05.375Z"}