{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:28:04Z","timestamp":1789424884911,"version":"build-2803163510"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH2010834"],"award-info":[{"award-number":["W81XWH2010834"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI151904"],"award-info":[{"award-number":["AI151904"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["1U01CK000512-01"],"award-info":[{"award-number":["1U01CK000512-01"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CBET-1928334"],"award-info":[{"award-number":["CBET-1928334"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R61AI174294"],"award-info":[{"award-number":["R61AI174294"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-21-1-0975"],"award-info":[{"award-number":["W81XWH-21-1-0975"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI163857"],"award-info":[{"award-number":["AI163857"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tick-borne spotted fever rickettsioses (SFRs) continue to cause severe illness and death in otherwise-healthy individuals due to lack of a timely and reliable diagnostic laboratory test. We recently identified a diagnostic biomarker for SFRs, the putative N-acetylmuramoyl-l-alanine amidase RC0497. Here, we developed a prototype laboratory test that targets RC0497 for diagnosis of SFRs. The concentrations of RC0497 in sera of <jats:italic>Rickettsia rickettsii<\/jats:italic>-infected guinea pigs and <jats:italic>R<\/jats:italic>. <jats:italic>conorii<\/jats:italic>-infected mice were determined by stable isotope dilution\u2013parallel reaction monitoring mass spectrometry (SID-PRM-MS), ranging from 0.1 to 1.1 ng\/ml. Using europium chelate nanoparticle reporters, we developed a lateral flow assay (LFA) and evaluated the test with a panel of serum samples of mock and experimentally infected animals. Interestingly, 21 of 22 (95.5%) serum samples from <jats:italic>R<\/jats:italic>. <jats:italic>rickettsii<\/jats:italic>-infected guinea pigs and <jats:italic>R<\/jats:italic>. <jats:italic>conorii<\/jats:italic>-infected mice yielded positive results with a ratio of test line \/ control line greater than the cutoff value determined for non-infected animals. All uninfected samples were in agreement with the intended results, suggesting that the initially assessed specificity of the test is 100%, among these samples. Mice infected with a lethal dose of <jats:italic>R<\/jats:italic>. <jats:italic>conorii<\/jats:italic> and treated with doxycycline on day 3 post-infection (p.i.), upon RC0497 detection by LFA, displayed significantly decreased rickettsial loads, comparable to the sublethal infection group on day 5 p.i.. A panel of human serum samples spiked with various concentrations of recombinant RC0497 were analyzed by LFA, suggesting that the limit of detection of the LFA was 0.64 ng\/mL. These findings suggest that the timely detection of RC0497 by a europium LFA offers guidance for treatment, leading to a significant improvement in infection outcomes. This work, for the first time, shows significant promise for a rapid and easy-to-use platform offering a timely diagnostic assay for severe SFRs.<\/jats:p>","DOI":"10.1371\/journal.pone.0312819","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T20:09:29Z","timestamp":1737144569000},"page":"e0312819","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Development of a rapid antigen-based lateral flow assay for tick-borne spotted fever 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