{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:32:46Z","timestamp":1781659966386,"version":"3.54.5"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI152208"],"award-info":[{"award-number":["R01AI152208"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI169287"],"award-info":[{"award-number":["R21AI169287"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI144136"],"award-info":[{"award-number":["R21AI144136"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R61AI179732"],"award-info":[{"award-number":["R61AI179732"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007259","name":"Stony Brook University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007259","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007539"],"award-info":[{"award-number":["T32AI007539"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Pathogenic <jats:italic>Rickettsia<\/jats:italic> species target vascular endothelial cells and cause systemic vasculitis. As obligate intracellular bacterial pathogens, <jats:italic>Rickettsia<\/jats:italic> must secure nutritional resources within the cytoplasm of endothelial cells while simultaneously subverting the innate immune defense system. With advances in rickettsial and host genetics, recent studies have identified novel molecular mechanisms involved in the complex interactions between <jats:italic>Rickettsia<\/jats:italic> and endothelial cells. However, it remains unclear how <jats:italic>Rickettsia<\/jats:italic> shields pathogen-derived immune stimulants, such as lipopolysaccharides (LPS) and peptidoglycan fragments, from immune recognition during intracellular replication. Prior work described two <jats:italic>Rickettsia conorii<\/jats:italic> variants with <jats:italic>kkaebi<\/jats:italic> transposon insertions in the <jats:italic>polysaccharide synthesis operon<\/jats:italic> (<jats:italic>pso<\/jats:italic>). Biochemical and immunological analyses revealed that <jats:italic>pso<\/jats:italic> is responsible for the biosynthesis of O-antigen (O-Ag) and the proper assembly of surface proteins. In the present work, we document that <jats:italic>pso<\/jats:italic> variant HK2 exhibits reduced capacities to adhere to and invade microvascular endothelial cells. Despite the low intracellular abundance, HK2 induced significantly higher levels of proinflammatory cytokines and chemokines, leading to premature cell death. Notably, HK2 exhibited defective intracellular survival in bone marrow-derived macrophages. This inability to dampen endothelial cell-mediated immune stimulation and resist macrophage-induced bactericidal activities resulted in the rapid elimination of viable <jats:italic>Rickettsia<\/jats:italic> in the mouse model of spotted fever. Further, when tested as a live-attenuated vaccine, HK2 elicited robust protective immunity against lethal spotted fever pathogenesis. Our work highlights the crucial role of <jats:italic>pso<\/jats:italic> in enabling <jats:italic>Rickettsia<\/jats:italic> to evade immune surveillance during intracellular replication within endothelial cells, ultimately delaying pathogen-induced programmed cell death and escaping immune defense mechanisms.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013277","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T17:57:53Z","timestamp":1750960673000},"page":"e1013277","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Polysaccharide synthesis operon modulates Rickettsia-endothelial cell interactions"],"prefix":"10.1371","volume":"21","author":[{"given":"Smruti","family":"Mishra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Helminiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9705","authenticated-orcid":true,"given":"Hwan Keun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"issue":"4","key":"ppat.1013277.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0002018","article-title":"Rickettsia phylogenomics: unwinding the intricacies of obligate intracellular life","volume":"3","author":"JJ Gillespie","year":"2008","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1013277.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6502a1","article-title":"Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - 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