{"entity": "researcher", "timestamp": "2026-07-20T13:36:02.171Z", "family": "Sixt", "given": "Barbara S", "initials": "BS", "orcid": "0000-0002-5607-8902", "affiliations": ["Department of Molecular Biology, Ume\u00e5 University , Ume\u00e5, Sweden.", "The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University , Ume\u00e5, Sweden.", "Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University , Ume\u00e5, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/998ac876b31f45c5b10d36f0d10c7390.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/998ac876b31f45c5b10d36f0d10c7390"}}, "publications": [{"entity": "publication", "iuid": "a97b36bc55b94119b54060180a6e6305", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a97b36bc55b94119b54060180a6e6305.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a97b36bc55b94119b54060180a6e6305"}}, "title": "Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply.", "authors": [{"family": "Babu Sait", "given": "Mohammed Rizwan", "initials": "MR"}, {"family": "Jachmann", "given": "Lana H", "initials": "LH"}, {"family": "T\u00fcrk\u00f6z", "given": "G\u00f6zde", "initials": "G"}, {"family": "Milivojevic", "given": "Milica", "initials": "M"}, {"family": "Llorente-S\u00e1ez", "given": "Celia", "initials": "C"}, {"family": "Dhanjal", "given": "Soniya", "initials": "S"}, {"family": "Schumacher", "given": "Fabian", "initials": "F"}, {"family": "Henriksson", "given": "Sara", "initials": "S", "orcid": "0000-0003-1615-0583", "researcher": {"href": "https://publications.scilifelab.se/researcher/934e6f18e3c94684be715e7bdc28d9b7.json"}}, {"family": "Gayathri Vegesna", "given": "Naga Venkata", "initials": "NV"}, {"family": "Seddik", "given": "Noha", "initials": "N"}, {"family": "Chaban", "given": "Anastasiia", "initials": "A"}, {"family": "Mohanty", "given": "Partha", "initials": "P"}, {"family": "\u00d6lander", "given": "Magnus", "initials": "M"}, {"family": "Muraleedharan", "given": "Samada", "initials": "S"}, {"family": "Farmand Azadeh", "given": "Sepideh", "initials": "S"}, {"family": "Kleuser", "given": "Burkhard", "initials": "B"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Sixt", "given": "Barbara S", "initials": "BS", "orcid": "0000-0002-5607-8902", "researcher": {"href": "https://publications.scilifelab.se/researcher/998ac876b31f45c5b10d36f0d10c7390.json"}}], "type": "journal article", "published": "2025-08-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "issn-l": "1544-9173", "volume": "23", "issue": "8", "pages": "e3003297"}, "abstract": "A mechanistic understanding of how intracellular pathogens evade the intrinsic defenses of their host cells could open up intriguing therapeutic opportunities. Here, we applied a genome-wide genetic screening approach to investigate the nature of the defensive host cell death response suppressed by the membrane trafficking modulator CpoS, an effector protein secreted by the obligate intracellular bacterial pathogen Chlamydia trachomatis. Initially, this work revealed a CpoS-deficient mutant to exhibit a markedly increased dependence on host cellular synthesis of ceramides, the precursors of complex sphingolipids. Using novel microscopic reporters, we then established CpoS' role in defense evasion to occur by preserving the integrity of Chlamydia's parasitophorous vacuole (the inclusion) via ensuring an adequate sphingolipid supply. More specifically, we observed CpoS deficiency to destabilize inclusions, initially characterized by a release of individual bacteria into the host cell cytosol, then followed by inclusion rupture concomitant with host cell death. Exogenous addition of sphingosine stabilized CpoS-deficient inclusions, whereas disruption of host cellular ceramide synthesis destabilized wild-type inclusions. In combination, CpoS deficiency and impaired ceramide synthesis - presumably disrupting both Chlamydia's vesicular and non-vesicular sphingolipid supply routes - destabilized inclusions even earlier, resulting in infection clearance and host cell survival rather than host cell death. Overall, this study highlights how the vacuolar pathogen C. trachomatis maintains vacuole integrity by ensuring a steady sphingolipid supply, potentially offering inspiration and directions for future therapeutic strategies targeting parasitophorous vacuoles.", "doi": "10.1371/journal.pbio.3003297", "pmid": "40794560", "labels": {"CRISPR Functional Genomics": "Collaborative", "Integrated Microscopy Technologies Ume\u00e5": "Technology development", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service", "Chemical Biology Consortium Sweden": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12342332"}, {"db": "pii", "key": "PBIOLOGY-D-24-02720"}], "notes": [], "created": "2025-09-04T09:04:13.790Z", "modified": "2026-03-18T09:37:39.227Z"}, {"entity": "publication", "iuid": "f44c3247c6294ee6a38e50b6c3afe7bc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f44c3247c6294ee6a38e50b6c3afe7bc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f44c3247c6294ee6a38e50b6c3afe7bc"}}, "title": "A multi-strategy antimicrobial discovery approach reveals new ways to treat Chlamydia.", "authors": [{"family": "\u00d6lander", "given": "Magnus", "initials": "M"}, {"family": "Rea V\u00e1zquez", "given": "Daniel", "initials": "D"}, {"family": "Meier", "given": "Karsten", "initials": "K"}, {"family": "Singh", "given": "Aakriti", "initials": "A"}, {"family": "Silva de Sousa", "given": "Amanda", "initials": "A"}, {"family": "Pu\u00e9rtolas-Balint", "given": "Fabiola", "initials": "F"}, {"family": "Milivojevic", "given": "Milica", "initials": "M"}, {"family": "Mooij", "given": "Lieke", "initials": "L"}, {"family": "Fredlund", "given": "Johanna", "initials": "J"}, {"family": "Calpe Bosch", "given": "Eduard", "initials": "E"}, {"family": "Ray\u00f3n D\u00edaz", "given": "Mar\u00eda", "initials": "M"}, {"family": "Lundgren", "given": "Moa", "initials": "M"}, {"family": "van der Wal", "given": "Karin", "initials": "K"}, {"family": "Zhu", "given": "Shaochun", "initials": "S"}, {"family": "Mateus", "given": "Andr\u00e9", "initials": "A"}, {"family": "Schroeder", "given": "Bjoern O", "initials": "BO"}, {"family": "Lohman", "given": "Jeremy R", "initials": "JR"}, {"family": "Sixt", "given": "Barbara S", "initials": "BS", "orcid": "0000-0002-5607-8902", "researcher": {"href": "https://publications.scilifelab.se/researcher/998ac876b31f45c5b10d36f0d10c7390.json"}}], "type": "journal article", "published": "2025-04-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "volume": "23", "issue": "4", "pages": "e3003123", "issn-l": "1544-9173"}, "abstract": "While the excessive use of broad-spectrum antibiotics is a major driver of the global antibiotic resistance crisis, more selective therapies remain unavailable for the majority of bacterial pathogens. This includes the obligate intracellular bacterial pathogens of the genus Chlamydia, which cause millions of urogenital, ocular, and respiratory infections each year. Conducting a comprehensive search of the chemical space for novel antichlamydial activities, we identified over 60 compounds that are chemically diverse, structurally distinct from known antibiotics, non-toxic to human cells, and highly potent in preventing the growth of Chlamydia trachomatis in cell cultures. Some blocked C. trachomatis development reversibly, while others eradicated both established and persistent infections in a bactericidal manner. The top molecules displayed compelling selectivity, yet broad activity against diverse Chlamydia strains and species, including both urogenital and ocular serovars of C. trachomatis, as well as Chlamydia muridarum and Chlamydia caviae. Some compounds also displayed synergies with clinically used antibiotics. Critically, we found the most potent antichlamydial compound to inhibit fatty acid biosynthesis via covalent binding to the active site of Chlamydia FabH, identifying a new mechanism of FabH inhibition and highlighting a possible way to selectively treat Chlamydia infections.", "doi": "10.1371/journal.pbio.3003123", "pmid": "40299795", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12040169"}, {"db": "pii", "key": "PBIOLOGY-D-25-00637"}], "notes": [], "created": "2026-02-23T09:07:47.582Z", "modified": "2026-02-23T09:07:47.690Z"}, {"entity": "publication", "iuid": "aa7cdea45678475ca4310179b0f37df0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa7cdea45678475ca4310179b0f37df0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa7cdea45678475ca4310179b0f37df0"}}, "title": "A multi-strategy antimicrobial discovery approach reveals new ways to combatChlamydia", "authors": [{"family": "\u00d6lander", "given": "Magnus", "initials": "M"}, {"family": "V\u00e1zquez", "given": "Daniel Rea", "initials": "DR"}, {"family": "Meier", "given": "Karsten", "initials": "K"}, {"family": "Mooij", "given": "Lieke", "initials": "L"}, {"family": "Fredlund", "given": "Johanna", "initials": "J"}, {"family": "Pu\u00e9rtolas-Balint", "given": "Fabiola", "initials": "F", "orcid": "0000-0003-4898-5673", "researcher": {"href": "https://publications.scilifelab.se/researcher/52b9ecd971f64eb89d05334fe9e975bb.json"}}, {"family": "Calpe", "given": "Eduard", "initials": "E"}, {"family": "D\u00edaz", "given": "Mar\u00eda Ray\u00f3n", "initials": "MR"}, {"family": "van der Wal", "given": "Karin", "initials": "K"}, {"family": "Schroeder", "given": "Bjoern O", "initials": "BO", "orcid": "0000-0002-6716-8284", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2c57653fc214cbcbb242cbbc524d517.json"}}, {"family": "Sixt", "given": "Barbara Susanne", "initials": "BS", "orcid": "0000-0002-5607-8902", "researcher": {"href": "https://publications.scilifelab.se/researcher/998ac876b31f45c5b10d36f0d10c7390.json"}}], "type": "posted-content", "published": "2023-11-30", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2023.11.30.569351", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [], "notes": [], "created": "2024-01-22T08:01:55.831Z", "modified": "2025-12-18T19:40:37.733Z"}, {"entity": "publication", "iuid": "fd3e6d7a2fa64dbd919e50d58ee695c4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fd3e6d7a2fa64dbd919e50d58ee695c4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fd3e6d7a2fa64dbd919e50d58ee695c4"}}, "title": "The Chlamydia effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35.", "authors": [{"family": "Meier", "given": "Karsten", "initials": "K"}, {"family": "Jachmann", "given": "Lana H", "initials": "LH"}, {"family": "T\u00fcrk\u00f6z", "given": "G\u00f6zde", "initials": "G"}, {"family": "Babu Sait", "given": "Mohammed Rizwan", "initials": "MR"}, {"family": "P\u00e9rez", "given": "Luc\u00eda", "initials": "L"}, {"family": "Kepp", "given": "Oliver", "initials": "O"}, {"family": "Valdivia", "given": "Raphael H", "initials": "RH"}, {"family": "Kroemer", "given": "Guido", "initials": "G"}, {"family": "Sixt", "given": "Barbara S", "initials": "BS", "orcid": "0000-0002-5607-8902", "researcher": {"href": "https://publications.scilifelab.se/researcher/998ac876b31f45c5b10d36f0d10c7390.json"}}], "type": "journal article", "published": "2023-08-31", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "14", "issue": "4", "pages": "e0319022", "issn-l": null}, "abstract": "The obligate intracellular bacterium Chlamydia trachomatis inserts a family of inclusion membrane (Inc) proteins into the membrane of its vacuole (the inclusion). The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlying mechanism remained elusive. By complementing a cpoS mutant with various natural orthologs and variants of CpoS, we linked distinct molecular interactions of CpoS to distinct functions. Unexpectedly, we found CpoS to be essential for the formation of inclusion membrane microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. While the function of CpoS in microdomains was uncoupled from its role in the suppression of host cellular defenses, we found the ability of CpoS to interact with Rab GTPases to be required not only for the manipulation of membrane trafficking, such as to mediate transport of ceramide-derived lipids (sphingolipids) to the inclusion, but also for the inhibition of Stimulator of interferon genes (STING)-dependent type I interferon responses. Indeed, depletion of Rab35 phenocopied the exacerbated interferon responses observed during infection with CpoS-deficient mutants. Overall, our findings highlight the role of Inc-Inc interactions in shaping the inclusion microenvironment and the modulation of membrane trafficking as a pathogenic immune evasion strategy. IMPORTANCE Chlamydia trachomatis is a prevalent bacterial pathogen that causes blinding ocular scarring and urogenital infections that can lead to infertility and pregnancy complications. Because Chlamydia can only grow within its host cell, boosting the intrinsic defenses of human cells may represent a novel strategy to fight pathogen replication and survival. Hence, CpoS, a Chlamydia protein known to block host cellular defenses, or processes regulated by CpoS, could provide new opportunities for therapeutic intervention. By revealing CpoS as a multifunctional virulence factor and by linking its ability to block host cellular immune signaling to the modulation of membrane trafficking, the present work may provide a foundation for such rationale targeting and advances our understanding of how intracellular bacteria can shape and protect their growth niche.", "doi": "10.1128/mbio.03190-22", "pmid": "37530528", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10470785"}], "notes": [], "created": "2023-10-18T18:36:48.383Z", "modified": "2025-10-17T13:04:27.583Z"}]}