{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T19:03:48Z","timestamp":1763060628022,"version":"3.45.0"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","award":["Fundamental Fund: fiscal year 2024 by National Science Research and Innovation Fund (NSRF)"],"award-info":[{"award-number":["Fundamental Fund: fiscal year 2024 by National Science Research and Innovation Fund (NSRF)"]}],"id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Malaria remains a major global health challenge, caused by several\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    species and transmitted via mosquito vectors. Among these,\n                    <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                    is notable for its zoonotic nature, capable of infecting both macaques and humans. The incidence of\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    infections has been rising, particularly in Southeast Asia, raising public health concerns. However, compared to other\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    species, the biology, pathophysiology, and transmission dynamics of\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    remain poorly understood. Given the absence of a licensed vaccine and the increasing threat of drug resistance, a deeper understanding of\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    biology is essential for effective control and management strategies. This study investigates the metabolomic landscape of\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    across three intraerythrocytic stagesring, trophozoite, and schizont using mass spectrometry-based metabolomics to gain insights into parasite biology. The analysis revealed distinct metabolic profiles, particularly in the ring stage compared to the other two stages. While glycerophospholipid metabolism and sphingolipid de novo biosynthesis emerged as key pathways associated with common metabolites across all stages, phosphatidylserine synthesis was specifically linked to ring-stage-biased metabolites. Notably, CDP-diacylglycerol-inositol 3-phosphatidyltransferase was highlighted as a promising target based on shared and stage-biased metabolites. Collectively, our findings offer a comprehensive metabolomic profile of\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    blood-stage development, enhancing our understanding of its biology and identifying potential drug targets that could support the development of novel therapeutic strategies against\n                    <jats:italic>P. knowlesi<\/jats:italic>\n                    malaria.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0337058","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:49:55Z","timestamp":1763059795000},"page":"e0337058","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mass spectrometry-based metabolomics uncovers distinct metabolic signatures and potential therapeutic targets in Plasmodium knowlesi"],"prefix":"10.1371","volume":"20","author":[{"given":"Naphatsamon","family":"Uthailak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadudee","family":"Chotirat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ammarind","family":"Anatjitsupha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waraporn","family":"Thongyod","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4691-7063","authenticated-orcid":true,"given":"Phornpimon","family":"Tipthara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jetsumon","family":"Sattabongkot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Nguitragool","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1154-6485","authenticated-orcid":true,"given":"Onrapak","family":"Reamtong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"pone.0337058.ref001","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.2147\/IDR.S405668","article-title":"Malaria: An Overview","volume":"16","author":"M Fikadu","year":"2023","journal-title":"Infect Drug Resist"},{"key":"pone.0337058.ref002","doi-asserted-by":"crossref","DOI":"10.30875\/9789287076717","volume-title":"World malaria report 2024","author":"World Health Organization","year":"2024"},{"key":"pone.0337058.ref003","volume-title":"Malaria parasites and other Haemosporidia","author":"PC Garnham","year":"1967"},{"issue":"1","key":"pone.0337058.ref004","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/s12936-017-2044-0","article-title":"Species and genotype diversity of Plasmodium in malaria patients from Gabon analysed by next generation sequencing","volume":"16","author":"A Lalremruata","year":"2017","journal-title":"Malar J"},{"key":"pone.0337058.ref005","doi-asserted-by":"crossref","first-page":"17050","DOI":"10.1038\/nrdp.2017.50","article-title":"Malaria","volume":"3","author":"MA Phillips","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"pone.0337058.ref006","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1128\/CMR.00079-12","article-title":"Human infections and detection of Plasmodium knowlesi","volume":"26","author":"B Singh","year":"2013","journal-title":"Clin Microbiol Rev"},{"issue":"10","key":"pone.0337058.ref007","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3390\/tropicalmed8100478","article-title":"Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells","volume":"8","author":"RP Jajosky","year":"2023","journal-title":"Trop Med Infect Dis"},{"issue":"3","key":"pone.0337058.ref008","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4269\/ajtmh.1968.17.355","article-title":"Experimental mosquito-transmission of Plasmodium knowlesi to man and monkey","volume":"17","author":"W Chin","year":"1968","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"pone.0337058.ref009","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12936-022-04110-z","article-title":"Is there evidence of sustained human-mosquito-human transmission of the zoonotic malaria Plasmodium knowlesi? 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