{"entity": "researcher", "timestamp": "2026-07-19T06:40:19.284Z", "family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "affiliations": ["Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University, 90187 Ume\u00e5, Sweden.", "Department of Molecular Biology, Ume\u00e5 University, 90187 Ume\u00e5, Sweden.", "The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, 90187 Ume\u00e5, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f"}}, "publications": [{"entity": "publication", "iuid": "c45c714869d64a00996f49c14d6bedab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c45c714869d64a00996f49c14d6bedab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c45c714869d64a00996f49c14d6bedab"}}, "title": "Minor hemolysin-coregulated proteins (Hcp) form heteromeric complexes and mediate effector secretion in Bacteroidales type VI secretion systems.", "authors": [{"family": "San-Miguel", "given": "Sergio G", "initials": "SG"}, {"family": "Hillier", "given": "Jessica B", "initials": "JB"}, {"family": "Saleh Al-Ammari", "given": "Manal Kamal", "initials": "MK"}, {"family": "Johansson", "given": "Emma", "initials": "E"}, {"family": "Kowalska", "given": "Anna", "initials": "A"}, {"family": "Sauer", "given": "Uwe", "initials": "U", "orcid": "0000-0002-3420-439X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d011e944ae54d47aed374d548007812.json"}}, {"family": "Batista", "given": "Paulo Ricardo", "initials": "PR"}, {"family": "Sandblad", "given": "Linda", "initials": "L", "orcid": "0000-0003-3492-3287", "researcher": {"href": "https://publications.scilifelab.se/researcher/070825e0190a4e9a932e79663d2bc89f.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Cisneros", "given": "David A", "initials": "DA", "orcid": "0000-0001-9919-0075", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f7a4aba7af436899b5d63f95f0dcda.json"}}], "type": "journal article", "published": "2026-04-16", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "pages": "111464", "volume": "302", "issue": "6", "issn-l": "0021-9258"}, "abstract": "The type VI secretion system (T6SS) is a protein complex found in Gram-negative bacteria that mediates intercellular antagonism. Hemolysin-coregulated proteins (Hcp) are major structural proteins in these systems. Hcp forms hexameric rings that stack to create an inner tube structure essential for translocating effector proteins into target cells. In gut Bacteroidales, T6SS loci encode multiple Hcp proteins with unknown function. The gut commensal Bacteroides fragilis encodes five Hcp subunits (sHcp and Hcp1-4) that have low sequence similarity. In this study, we investigated the roles of these proteins. Interaction studies showed that sHcp forms homohexamers, which is consistent with a major role of forming the bulk of the inner tube. In contrast, the less abundant minor Hcp1-4 were shown to form an interaction network involving heteromeric complexes. Biochemical and genetic analyses demonstrated that Hcp1 and Hcp2 assemble into heterohexamers and that this complex recognizes the secreted effector Bte1, contributing to its secretion. Finally, we showed that Hcp modules, which are encoded in highly syntenic regions in T6SS loci of Bacteroidales, cluster with effectors. These results imply that the minor Hcps genetically cosegregate with cognate effectors, contributing to effector cassette variability. Thus, minor Hcp subunits function as recognition particles for effectors to mediate secretion, which appears to be a conserved trait in Bacteroidales T6SSs. Exploiting these features could facilitate the characterization of unknown effectors by copurifying them with their cognate Hcps. This approach may reveal new insights into bacterial interactions and the mechanisms that establish gut biodiversity.", "doi": "10.1016/j.jbc.2026.111464", "pmid": "41999889", "labels": {"Structural Proteomics": "Service", "Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC13213661"}, {"db": "pii", "key": "S0021-9258(26)00336-4"}], "notes": [], "created": "2026-04-24T08:57:10.339Z", "modified": "2026-06-24T09:47:35.264Z"}, {"entity": "publication", "iuid": "f8ebe7efa7b642fe889dab9c051a3e5e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8ebe7efa7b642fe889dab9c051a3e5e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8ebe7efa7b642fe889dab9c051a3e5e"}}, "title": "Antiparallel stacking of Csu pili drives Acinetobacter baumannii 3D biofilm assembly", "authors": [{"family": "Malmi", "given": "Henri", "initials": "H", "orcid": "0000-0001-9872-8523", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a082b1f8b334faca225e6000daabcf9.json"}}, {"family": "Pakharukova", "given": "Natalia", "initials": "N", "orcid": "0000-0002-8363-6105", "researcher": {"href": "https://publications.scilifelab.se/researcher/555b7be2f9ba46a9b78549d89e69b41b.json"}}, {"family": "Paul", "given": "Bindusmita", "initials": "B", "orcid": "0000-0001-9844-9751", "researcher": {"href": "https://publications.scilifelab.se/researcher/1667be16b3c947a2a35eb58ee357868a.json"}}, {"family": "Tuittila", "given": "Minna", "initials": "M"}, {"family": "Ahmad", "given": "Irfan", "initials": "I"}, {"family": "Knight", "given": "Stefan David", "initials": "SD", "orcid": "0000-0002-7180-8758", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9971d1ebb542a8b54601675c3869f5.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Ghosal", "given": "Debnath", "initials": "D", "orcid": "0000-0002-2227-0330", "researcher": {"href": "https://publications.scilifelab.se/researcher/d50f9497285b4b709f1011366d074f2a.json"}}, {"family": "Zavialov", "given": "Anton V", "initials": "AV", "orcid": "0000-0001-6191-5931", "researcher": {"href": "https://publications.scilifelab.se/researcher/79863c4e5ca94dffa0103c111a5da35c.json"}}], "type": "journal-article", "published": "2026-02-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "issn-l": "2041-1723"}, "abstract": null, "doi": "10.1038/s41467-026-68860-z", "pmid": null, "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service", "Cryo-EM": "Service"}, "xrefs": [], "notes": [], "created": "2026-06-24T09:43:26.636Z", "modified": "2026-06-24T09:43:26.992Z"}, {"entity": "publication", "iuid": "bc0935a69afd4244a818a5f794c2d7e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bc0935a69afd4244a818a5f794c2d7e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bc0935a69afd4244a818a5f794c2d7e7"}}, "title": "Bacteroidales T6SS minor Hcp subunits form heteromers recognising effectors", "authors": [{"family": "San-Miguel", "given": "Sergio G", "initials": "SG"}, {"family": "Al-Ammari", "given": "Manal Kamal Saleh", "initials": "MKS"}, {"family": "Johansson", "given": "Emma", "initials": "E"}, {"family": "Kowalska", "given": "Anna", "initials": "A"}, {"family": "Sauer", "given": "Uwe", "initials": "U", "orcid": "0000-0002-3420-439X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d011e944ae54d47aed374d548007812.json"}}, {"family": "Batista", "given": "Paulo Ricardo", "initials": "PR"}, {"family": "Sandblad", "given": "Linda", "initials": "L", "orcid": "0000-0003-3492-3287", "researcher": {"href": "https://publications.scilifelab.se/researcher/070825e0190a4e9a932e79663d2bc89f.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Cisneros", "given": "David A", "initials": "DA", "orcid": "0000-0001-9919-0075", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f7a4aba7af436899b5d63f95f0dcda.json"}}], "type": "posted-content", "published": "2025-01-10", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.01.09.632221", "pmid": null, "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-11-17T11:25:11.604Z", "modified": "2025-12-18T19:23:20.382Z"}, {"entity": "publication", "iuid": "140ad3700ed54931ac2a2d7ab9429d34", "links": {"self": {"href": "https://publications.scilifelab.se/publication/140ad3700ed54931ac2a2d7ab9429d34.json"}, "display": {"href": "https://publications.scilifelab.se/publication/140ad3700ed54931ac2a2d7ab9429d34"}}, "title": "Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in Acinetobacter baumannii.", "authors": [{"family": "Mushtaq", "given": "Fizza", "initials": "F"}, {"family": "Nadeem", "given": "Aftab", "initials": "A", "orcid": "0000-0002-1439-6216", "researcher": {"href": "https://publications.scilifelab.se/researcher/a672dd942f9b4ba0880210a8c7358227.json"}}, {"family": "Yabrag", "given": "Abdelbasset", "initials": "A"}, {"family": "Bala", "given": "Anju", "initials": "A"}, {"family": "Karah", "given": "Nabil", "initials": "N", "orcid": "0000-0001-8867-658X", "researcher": {"href": "https://publications.scilifelab.se/researcher/57d9242e1afb4e90917ba5e5a2ddfba0.json"}}, {"family": "Zlatkov", "given": "Nikola", "initials": "N", "orcid": "0000-0003-3318-9084", "researcher": {"href": "https://publications.scilifelab.se/researcher/c76ab107ec0e421b8b3d51f1807a0b9c.json"}}, {"family": "Nyunt Wai", "given": "Sun", "initials": "S", "orcid": "0000-0003-4793-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/261986c5cf8f48878b74c4f60cc7af69.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Ahmad", "given": "Irfan", "initials": "I", "orcid": "0000-0002-2648-1952", "researcher": {"href": "https://publications.scilifelab.se/researcher/72e82b9d27f44efe9302cb486a637c8e.json"}}], "type": "journal article", "published": "2024-02-06", "journal": {"title": "Microbiol Spectr", "issn": "2165-0497", "pages": "e0295623", "volume": "12", "issue": "2", "issn-l": null}, "abstract": "Carbapenem-resistant Acinetobacter baumannii causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant A. baumannii. Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by A. baumannii AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline. Using a variety of microscopic techniques, we demonstrate that extracellular polysaccharide moieties mediate colistin tolerance to opaque A. baumannii at single-cell level and that mushroom-shaped biofilm structures protect opaque bacteria at the community level. The colony switch phenotype is found to alter several traits of A. baumannii, including long-term survival under desiccation, tolerance to ethanol, competition with Escherichia coli, and intracellular survival in the environmental model host Acanthamoeba castellanii. Additionally, our findings suggest that extracellular DNA associated with membrane vesicles can promote colony switching in a DNA recombinase-dependent manner.IMPORTANCEAs a WHO top-priority drug-resistant microbe, Acinetobacter baumannii significantly contributes to hospital-associated infections worldwide. One particularly intriguing aspect is its ability to reversibly switch its colony morphotype on agar plates, which has been remarkably underexplored. In this study, we employed various microscopic techniques and phenotypic assays to investigate the colony phase variation switch under different clinically and environmentally relevant conditions. Our findings reveal that the presence of a poly N-acetylglucosamine-positive extracellular matrix layer contributes to the protection of bacteria from the bactericidal effects of colistin. Furthermore, we provide intriguing insights into the multicellular lifestyle of A. baumannii, specifically in the context of colony switch variation within its predatory host, Acanthamoeba castellanii.", "doi": "10.1128/spectrum.02956-23", "pmid": "38205963", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10845969"}], "notes": [], "created": "2024-01-12T12:05:10.542Z", "modified": "2024-11-27T11:11:47.957Z"}, {"entity": "publication", "iuid": "d6798b4045e54b48806da2a7a38f20e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d6798b4045e54b48806da2a7a38f20e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d6798b4045e54b48806da2a7a38f20e2"}}, "title": "Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii.", "authors": [{"family": "Ahmad", "given": "Irfan", "initials": "I", "orcid": "0000-0002-0470-190X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8af3e35a77074743a121e9c53e7d1573.json"}}, {"family": "Nadeem", "given": "Aftab", "initials": "A"}, {"family": "Mushtaq", "given": "Fizza", "initials": "F"}, {"family": "Zlatkov", "given": "Nikola", "initials": "N"}, {"family": "Shahzad", "given": "Muhammad", "initials": "M"}, {"family": "Zavialov", "given": "Anton V", "initials": "AV"}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN", "orcid": "0000-0003-4793-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/261986c5cf8f48878b74c4f60cc7af69.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}], "type": "journal article", "published": "2023-12-14", "journal": {"title": "NPJ Biofilms Microbiomes", "issn": "2055-5008", "volume": "9", "issue": "1", "pages": "101", "issn-l": "2055-5008"}, "abstract": "Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.", "doi": "10.1038/s41522-023-00465-6", "pmid": "38097635", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10721868"}, {"db": "pii", "key": "10.1038/s41522-023-00465-6"}], "notes": [], "created": "2024-01-12T12:00:45.570Z", "modified": "2024-01-12T12:00:45.834Z"}, {"entity": "publication", "iuid": "84be06817c144739a3b32c8d33eb25f2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/84be06817c144739a3b32c8d33eb25f2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/84be06817c144739a3b32c8d33eb25f2"}}, "title": "Archaic chaperone-usher pili self-secrete into superelastic zigzag springs.", "authors": [{"family": "Pakharukova", "given": "Natalia", "initials": "N", "orcid": "0000-0002-8363-6105", "researcher": {"href": "https://publications.scilifelab.se/researcher/555b7be2f9ba46a9b78549d89e69b41b.json"}}, {"family": "Malmi", "given": "Henri", "initials": "H", "orcid": "0000-0001-9872-8523", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a082b1f8b334faca225e6000daabcf9.json"}}, {"family": "Tuittila", "given": "Minna", "initials": "M"}, {"family": "Dahlberg", "given": "Tobias", "initials": "T"}, {"family": "Ghosal", "given": "Debnath", "initials": "D"}, {"family": "Chang", "given": "Yi-Wei", "initials": "YW", "orcid": "0000-0003-2391-473X", "researcher": {"href": "https://publications.scilifelab.se/researcher/53c3646339b4487aa76fa4fb6503e14c.json"}}, {"family": "Myint", "given": "Si Lhyam", "initials": "SL"}, {"family": "Paavilainen", "given": "Sari", "initials": "S"}, {"family": "Knight", "given": "Stefan David", "initials": "SD", "orcid": "0000-0002-7180-8758", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9971d1ebb542a8b54601675c3869f5.json"}}, {"family": "Lamminm\u00e4ki", "given": "Urpo", "initials": "U"}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Andersson", "given": "Magnus", "initials": "M", "orcid": "0000-0002-9835-3263", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe860af5d944447086cbf2d00e3beb3e.json"}}, {"family": "Jensen", "given": "Grant", "initials": "G", "orcid": "0000-0003-1556-4864", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fdad82f6f3e41e8ad427f8d2b5b0d0b.json"}}, {"family": "Zavialov", "given": "Anton V", "initials": "AV", "orcid": "0000-0001-6191-5931", "researcher": {"href": "https://publications.scilifelab.se/researcher/79863c4e5ca94dffa0103c111a5da35c.json"}}], "type": "journal article", "published": "2022-09-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "609", "issue": "7926", "pages": "335-340", "issn-l": "0028-0836"}, "abstract": "Adhesive pili assembled through the chaperone-usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria1-3. Archaic chaperone-usher pathway pili, the most diverse and widespread chaperone-usher pathway adhesins, are promising vaccine and drug targets owing to their prevalence in the most troublesome multidrug-resistant pathogens1,4,5. However, their architecture and assembly-secretion process remain unknown. Here, we present the cryo-electron microscopy structure of the prototypical archaic Csu pilus that mediates biofilm formation of Acinetobacter baumannii-a notorious multidrug-resistant nosocomial pathogen. In contrast to the thick helical tubes of the classical type 1 and P pili, archaic pili assemble into an ultrathin zigzag architecture secured by an elegant clinch mechanism. The molecular clinch provides the pilus with high mechanical stability as well as superelasticity, a property observed for the first time, to our knowledge, in biomolecules, while enabling a more economical and faster pilus production. Furthermore, we demonstrate that clinch formation at the cell surface drives pilus secretion through the outer membrane. These findings suggest that clinch-formation inhibitors might represent a new strategy to fight multidrug-resistant bacterial infections.", "doi": "10.1038/s41586-022-05095-0", "pmid": "35853476", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9452303"}, {"db": "pii", "key": "10.1038/s41586-022-05095-0"}], "notes": [], "created": "2023-11-26T14:07:20.315Z", "modified": "2023-11-26T14:07:20.536Z"}, {"entity": "publication", "iuid": "8dea3c7c49ff4ef6b547b14d336676b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8dea3c7c49ff4ef6b547b14d336676b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8dea3c7c49ff4ef6b547b14d336676b2"}}, "title": "Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from Vibrio cholerae.", "authors": [{"family": "Nadeem", "given": "Aftab", "initials": "A", "orcid": "0000-0002-1439-6216", "researcher": {"href": "https://publications.scilifelab.se/researcher/a672dd942f9b4ba0880210a8c7358227.json"}}, {"family": "Berg", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-3609-2878", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1d5f2e44c4ab8bdd18c4b783f6dd4.json"}}, {"family": "Pace", "given": "Hudson", "initials": "H", "orcid": "0000-0001-5116-2577", "researcher": {"href": "https://publications.scilifelab.se/researcher/92ed46491f9147fc92388c6707204e92.json"}}, {"family": "Alam", "given": "Athar", "initials": "A", "orcid": "0000-0001-8773-7598", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d1da5164b7644b897ef05c40cec4606.json"}}, {"family": "Toh", "given": "Eric", "initials": "E", "orcid": "0000-0002-0103-0696", "researcher": {"href": "https://publications.scilifelab.se/researcher/70008894b990416fab9d4eb4627a3bc0.json"}}, {"family": "\u00c5d\u00e9n", "given": "J\u00f6rgen", "initials": "J", "orcid": "0000-0002-4480-1219", "researcher": {"href": "https://publications.scilifelab.se/researcher/00206abad0de45eb90dc6bd3d5f3cf22.json"}}, {"family": "Zlatkov", "given": "Nikola", "initials": "N", "orcid": "0000-0003-3318-9084", "researcher": {"href": "https://publications.scilifelab.se/researcher/c76ab107ec0e421b8b3d51f1807a0b9c.json"}}, {"family": "Myint", "given": "Si Lhyam", "initials": "SL", "orcid": "0000-0001-5384-3691", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec5ca92bae3a4dfab72f4a44d29f5a18.json"}}, {"family": "Persson", "given": "Karina", "initials": "K", "orcid": "0000-0003-0807-0348", "researcher": {"href": "https://publications.scilifelab.se/researcher/75b999cf004141468eefb2504b7c5b99.json"}}, {"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}, {"family": "Sj\u00f6stedt", "given": "Anders", "initials": "A", "orcid": "0000-0002-0768-8405", "researcher": {"href": "https://publications.scilifelab.se/researcher/52b15132704f48609be086c9d256cb14.json"}}, {"family": "Bally", "given": "Marta", "initials": "M", "orcid": "0000-0002-5865-8302", "researcher": {"href": "https://publications.scilifelab.se/researcher/923521b36e7746a3979801d0502eb6a9.json"}}, {"family": "Barandun", "given": "Jonas", "initials": "J", "orcid": "0000-0003-2971-8190", "researcher": {"href": "https://publications.scilifelab.se/researcher/2456fbe0b6bf406889842ab9f0267c22.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN", "orcid": "0000-0003-4793-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/261986c5cf8f48878b74c4f60cc7af69.json"}}], "type": "journal article", "published": "2022-02-08", "journal": {"title": "Elife", "issn": "2050-084X", "issn-l": "2050-084X", "volume": "11", "issue": null, "pages": null}, "abstract": "The \u03b1-pore-forming toxins (\u03b1-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an \u03b1-PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other \u03b1-PFTs. In contrast, MakA in isolation induces tube-like structures in acidic endosomal compartments of epithelial cells in vitro. The present study unravels the dynamics of tubular growth, which occurs in a pH-, lipid-, and concentration-dependent manner. Within acidified organelle lumens or when incubated with cells in acidic media, MakA forms oligomers and remodels membranes into high-curvature tubes leading to loss of membrane integrity. A 3.7 \u00c5 cryo-electron microscopy structure of MakA filaments reveals a unique protein-lipid superstructure. MakA forms a pinecone-like spiral with a central cavity and a thin annular lipid bilayer embedded between the MakA transmembrane helices in its active \u03b1-PFT conformation. Our study provides insights into a novel tubulation mechanism of an \u03b1-PFT protein and a new mode of action by a secreted bacterial toxin.", "doi": "10.7554/eLife.73439", "pmid": "35131030", "labels": {"Cryo-EM": "Service", "Integrated Microscopy Technologies Ume\u00e5": "Service", "Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "73439"}, {"db": "pmc", "key": "PMC8824476"}], "notes": [], "created": "2022-02-09T07:49:59.081Z", "modified": "2025-10-17T13:03:55.018Z"}, {"entity": "publication", "iuid": "fdb4d8f046da44318cf95213df74e7b7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fdb4d8f046da44318cf95213df74e7b7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fdb4d8f046da44318cf95213df74e7b7"}}, "title": "A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion.", "authors": [{"family": "Nadeem", "given": "Aftab", "initials": "A", "orcid": "0000-0002-1439-6216", "researcher": {"href": "https://publications.scilifelab.se/researcher/a672dd942f9b4ba0880210a8c7358227.json"}}, {"family": "Nagampalli", "given": "Raghavendra", "initials": "R"}, {"family": "Toh", "given": "Eric", "initials": "E", "orcid": "0000-0002-0103-0696", "researcher": {"href": "https://publications.scilifelab.se/researcher/70008894b990416fab9d4eb4627a3bc0.json"}}, {"family": "Alam", "given": "Athar", "initials": "A", "orcid": "0000-0001-8773-7598", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d1da5164b7644b897ef05c40cec4606.json"}}, {"family": "Myint", "given": "Si Lhyam", "initials": "SL", "orcid": "0000-0001-5384-3691", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec5ca92bae3a4dfab72f4a44d29f5a18.json"}}, {"family": "Heidler", "given": "Thomas V", "initials": "TV", "orcid": "0000-0002-5997-3945", "researcher": {"href": "https://publications.scilifelab.se/researcher/54d1a40e92fc4128ab2477ccc717e7d8.json"}}, {"family": "Dongre", "given": "Mitesh", "initials": "M"}, {"family": "Zlatkov", "given": "Nikola", "initials": "N", "orcid": "0000-0003-3318-9084", "researcher": {"href": "https://publications.scilifelab.se/researcher/c76ab107ec0e421b8b3d51f1807a0b9c.json"}}, {"family": "Pace", "given": "Hudson", "initials": "H"}, {"family": "Bano", "given": "Fouzia", "initials": "F", "orcid": "0000-0003-0634-7091", "researcher": {"href": "https://publications.scilifelab.se/researcher/af79c94518a4488ea0bd314793eb808c.json"}}, {"family": "Sj\u00f6stedt", "given": "Anders", "initials": "A", "orcid": "0000-0002-0768-8405", "researcher": {"href": "https://publications.scilifelab.se/researcher/52b15132704f48609be086c9d256cb14.json"}}, {"family": "Bally", "given": "Marta", "initials": "M", "orcid": "0000-0002-5865-8302", "researcher": {"href": "https://publications.scilifelab.se/researcher/923521b36e7746a3979801d0502eb6a9.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN", "orcid": "0000-0003-4793-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/261986c5cf8f48878b74c4f60cc7af69.json"}}, {"family": "Persson", "given": "Karina", "initials": "K", "orcid": "0000-0003-0807-0348", "researcher": {"href": "https://publications.scilifelab.se/researcher/75b999cf004141468eefb2504b7c5b99.json"}}], "type": "journal article", "published": "2021-11-23", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "118", "issue": "47", "issn-l": "0027-8424"}, "abstract": "The protein MakA was discovered as a motility-associated secreted toxin from Vibrio cholerae Here, we show that MakA is part of a gene cluster encoding four additional proteins: MakB, MakC, MakD, and MakE. MakA, MakB, and MakE were readily detected in culture supernatants of wild-type V. cholerae, whereas secretion was very much reduced from a flagellum-deficient mutant. Crystal structures of MakA, MakB, and MakE revealed a structural relationship to a superfamily of bacterial pore-forming toxins. Expression of MakA/B/E in Escherichia coli resulted in toxicity toward Caenorhabditis elegans used as a predatory model organism. None of these Mak proteins alone or in pairwise combinations were cytolytic, but an equimolar mixture of MakA, MakB, and MakE acted as a tripartite cytolytic toxin in vitro, causing lysis of erythrocytes and cytotoxicity on cultured human colon carcinoma cells. Formation of oligomeric complexes on liposomes was observed by electron microscopy. Oligomer interaction with membranes was initiated by MakA membrane binding followed by MakB and MakE joining the assembly of a pore structure. A predicted membrane insertion domain of MakA was shown by site-directed mutagenesis to be essential for toxicity toward C. elegans Bioinformatic analyses revealed that the makCDBAE gene cluster is present as a genomic island in the vast majority of sequenced genomes of V. cholerae and the fish pathogen Vibrio anguillarum We suggest that the hitherto-unrecognized cytolytic MakA/B/E toxin can contribute to Vibrionaceae fitness and virulence potential in different host environments and organisms.", "doi": "10.1073/pnas.2111418118", "pmid": "34799450", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "2111418118"}, {"db": "pmc", "key": "PMC8617504"}], "notes": [], "created": "2022-04-01T16:02:49.616Z", "modified": "2022-04-01T16:02:49.767Z"}, {"entity": "publication", "iuid": "7250c61d4dbe4d34836ec68cafc81194", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7250c61d4dbe4d34836ec68cafc81194.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7250c61d4dbe4d34836ec68cafc81194"}}, "title": "Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy.", "authors": [{"family": "Corkery", "given": "Dale P", "initials": "DP", "orcid": "0000-0001-7930-0134", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e668ad5ea8458b8d0eebc3c653a62e.json"}}, {"family": "Nadeem", "given": "Aftab", "initials": "A", "orcid": "0000-0002-1439-6216", "researcher": {"href": "https://publications.scilifelab.se/researcher/a672dd942f9b4ba0880210a8c7358227.json"}}, {"family": "Aung", "given": "Kyaw Min", "initials": "KM", "orcid": "0000-0001-6898-0170", "researcher": {"href": "https://publications.scilifelab.se/researcher/e83f2522ab0f41309a9a427dfc1603fd.json"}}, {"family": "Hassan", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-1033-6830", "researcher": {"href": "https://publications.scilifelab.se/researcher/25960b28d4784ee8a4cb6faf5fc3f30e.json"}}, {"family": "Liu", "given": "Tao", "initials": "T"}, {"family": "Cervantes-Rivera", "given": "Ram\u00f3n", "initials": "R", "orcid": "0000-0002-0984-6286", "researcher": {"href": "https://publications.scilifelab.se/researcher/30e27ef16d2e4c1dbb8081613d4edb1c.json"}}, {"family": "Lystad", "given": "Alf H\u00e5kon", "initials": "AH"}, {"family": "Wang", "given": "Hui", "initials": "H"}, {"family": "Persson", "given": "Karina", "initials": "K"}, {"family": "Puhar", "given": "Andrea", "initials": "A", "orcid": "0000-0002-9915-002X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6232d9c68f242d69f38745cbe89c8e0.json"}}, {"family": "Simonsen", "given": "Anne", "initials": "A"}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN", "orcid": "0000-0003-4793-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/261986c5cf8f48878b74c4f60cc7af69.json"}}, {"family": "Wu", "given": "Yao-Wen", "initials": "Y"}], "type": "journal article", "published": "2021-02-23", "journal": {"title": "J. Cell. Sci.", "issn": "1477-9137", "issn-l": "0021-9533", "volume": "134", "issue": "5", "pages": "jcs.252015"}, "abstract": "Autophagy plays an essential role in the defense against many microbial pathogens as a regulator of both innate and adaptive immunity. Some pathogens have evolved sophisticated mechanisms that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered Vibrio cholerae cytotoxin, motility-associated killing factor A (MakA). pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 (herein referring to MAP1LC3B) lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex, required for LC3 lipidation at the membranous aggregate, resulted in an inhibition of both canonical autophagy and autophagy-related processes, including the unconventional secretion of interleukin-1\u03b2 (IL-1\u03b2). These findings identify a novel mechanism of host autophagy modulation and immune modulation employed by V. cholerae during bacterial infection.", "doi": "10.1242/jcs.252015", "pmid": "33106317", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [{"db": "pii", "key": "jcs.252015"}], "notes": [], "created": "2020-12-10T11:24:04.597Z", "modified": "2022-04-01T08:04:48.259Z"}, {"entity": "publication", "iuid": "f14cba2314b74cebb473dab317adef9d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f14cba2314b74cebb473dab317adef9d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f14cba2314b74cebb473dab317adef9d"}}, "title": "Exploring the bacterial nano-universe.", "authors": [{"family": "S\u00f6derholm", "given": "Niklas", "initials": "N", "orcid": "0000-0003-3964-3751", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff74d1308e044d7f81ddbe1eb73cfd9c.json"}}, {"family": "Singh", "given": "Birendra", "initials": "B", "orcid": "0000-0002-7246-1442", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a37eae28b0b45678502b7be34dbae99.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Sandblad", "given": "Linda", "initials": "L", "orcid": "0000-0003-3492-3287", "researcher": {"href": "https://publications.scilifelab.se/researcher/070825e0190a4e9a932e79663d2bc89f.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Curr. Opin. Struct. Biol.", "issn": "1879-033X", "volume": "64", "issue": null, "pages": "166-173", "issn-l": "0959-440X"}, "abstract": "Since the days of the first acknowledged microscopist, Antonie van Leeuwenhoek, the 'animalcules', that is, bacteria and other microbes have been subject to increasingly detailed visualization. With the currently most sophisticated molecular imaging method; cryo electron tomography (Cryo-ET), we are reaching the milestone of being able to image an entire organism in a single dataset at nanometer resolution. Cryo-ET will enable the next revolution in our understanding of bacterial cells, their ultra-structure and intricate molecular nanomachines. Here, we highlight recent research discoveries based on constantly progressing technology developments. We discuss advantages and challenges of using Cryo-ET to visualize spatial structure of microorganisms and macromolecular complexes in their native environment.", "doi": "10.1016/j.sbi.2020.07.002", "pmid": "32846309", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0959-440X(20)30125-1"}], "notes": [], "created": "2020-12-10T11:09:02.691Z", "modified": "2021-11-10T12:46:53.752Z"}, {"entity": "publication", "iuid": "ea8d919bed0b413cbc71d9599b91f20b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea8d919bed0b413cbc71d9599b91f20b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea8d919bed0b413cbc71d9599b91f20b"}}, "title": "Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates.", "authors": [{"family": "Ahmad", "given": "Irfan", "initials": "I"}, {"family": "Karah", "given": "Nabil", "initials": "N"}, {"family": "Nadeem", "given": "Aftab", "initials": "A"}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN"}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}], "type": "journal article", "published": "2019-01-04", "journal": {"volume": "14", "issn": "1932-6203", "issue": "1", "pages": "e0210082", "title": "PLoS ONE", "issn-l": "1932-6203"}, "abstract": "Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types. Our findings demonstrated that these phenotypic alterations were mostly strain-specific. In general, the translucent subpopulations of A. baumannii produced more dense biofilms, were more piliated, and released larger amounts of outer membrane vesicles (OMVs). In addition, the translucent subpopulations caused reduced fertility of Caenorhabditis elegans. When assessed for effects on the immune response in RAW 264.7 macrophages, the OMVs isolated from opaque subpopulations of A. baumannii appeared to be more immunogenic than the OMVs from the translucent form. However, also the OMVs from the translucent subpopulations had the potential to evoke an immune response. Therefore, we suggest that OMVs may be considered for development of new immunotherapeutic treatments against A. baumannii infections.", "doi": "10.1371/journal.pone.0210082", "pmid": "30608966", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-18-25863"}, {"db": "pmc", "key": "PMC6319719"}], "notes": [], "created": "2020-01-08T09:29:21.281Z", "modified": "2021-06-21T13:44:00.168Z"}]}