{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:48:59Z","timestamp":1791384539191,"version":"4.3.3"},"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI169279"],"award-info":[{"award-number":["R21AI169279"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Plasmodium falciparum<\/jats:italic> undergoes sequestration within deep tissues of the human body, spanning multiple organ systems with differing oxygen (O<jats:sub>2<\/jats:sub>) concentrations. The parasite is exposed to an even greater range of O<jats:sub>2<\/jats:sub> concentrations as it transitions from the human to the mosquito host, suggesting a high level of plasticity as it navigates these different environments. In this review, we explore factors that may contribute to the parasite\u2019s response to different environmental O<jats:sub>2<\/jats:sub> concentrations, recognizing that there are likely multiple pieces to this puzzle. We first review O<jats:sub>2<\/jats:sub>-sensing mechanisms, which exist in other apicomplexans such as <jats:italic>Toxoplasma gondii<\/jats:italic> and consider whether similar systems could exist in <jats:italic>Plasmodium<\/jats:italic>. Next, we review morphological and functional changes in <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic>\u2019s mitochondrion during the asexual-to-sexual stage transition and discuss how these changes overlap with the parasite\u2019s access to O<jats:sub>2<\/jats:sub>. We then delve into reactive oxygen species (ROS) as ROS production is influenced by O<jats:sub>2<\/jats:sub> availability and oxidative stress impacts <jats:italic>Plasmodium<\/jats:italic> intraerythrocytic development. Lastly, given that the primary role of the red blood cell (RBC) is to deliver O<jats:sub>2<\/jats:sub> throughout the body, we discuss how changes in the oxygenation status of hemoglobin, the RBC\u2019s O<jats:sub>2<\/jats:sub>-carrying protein and key nutrient for <jats:italic>Plasmodium<\/jats:italic>, could also potentially impact the parasite\u2019s growth during intraerythrocytic development. This review also highlights studies that have investigated <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> biology under varying O<jats:sub>2<\/jats:sub> concentrations and covers technical aspects related to <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> cultivation in the lab, focusing on sources of technical variation that could alter the amount of dissolved O<jats:sub>2<\/jats:sub> encountered by cells during in vitro experiments. Lastly, we discuss how culture systems can better replicate in vivo heterogeneity with respect to O<jats:sub>2<\/jats:sub> gradients, propose ideas for further research in this area, and consider translational implications related to O<jats:sub>2<\/jats:sub> and malaria.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012514","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T17:45:36Z","timestamp":1726767936000},"page":"e1012514","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Understanding the significance of oxygen tension on the biology of Plasmodium falciparum blood stages: From the human body to the laboratory"],"prefix":"10.1371","volume":"20","author":[{"given":"Dinah S.","family":"Nahid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Coffey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K.","family":"Bei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5369-0215","authenticated-orcid":true,"given":"Regina Joice","family":"Cordy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,19]]},"reference":[{"issue":"2","key":"ppat.1012514.ref001","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3347\/kjp.2019.57.2.117","article-title":"Induction of Angiogenesis by Malarial Infection through Hypoxia Dependent Manner.","volume":"57","author":"MK Park","year":"2019","journal-title":"Korean J Parasitol"},{"issue":"5","key":"ppat.1012514.ref002","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1086\/526521","article-title":"Placental hypoxia during placental malaria","volume":"197","author":"P Boeuf","year":"2008","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1012514.ref003","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1462-5822.2005.00628.x","article-title":"The host cell transcription factor hypoxia-inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels","volume":"8","author":"W Spear","year":"2006","journal-title":"Cell Microbiol"},{"issue":"7","key":"ppat.1012514.ref004","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.tim.2022.01.002","article-title":"The battle for oxygen during bacterial and fungal infections","volume":"30","author":"AC Andr\u00e9","year":"2022","journal-title":"Trends Microbiol"},{"issue":"4","key":"ppat.1012514.ref005","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.tips.2012.01.005","article-title":"Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy","volume":"33","author":"GL Semenza","year":"2012","journal-title":"Trends Pharmacol Sci"},{"issue":"10","key":"ppat.1012514.ref006","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.pt.2021.05.001","article-title":"Deconstructing the parasite multiplication rate of Plasmodium falciparum","volume":"37","author":"B Gnangnon","year":"2021","journal-title":"Trends Parasitol"},{"issue":"2","key":"ppat.1012514.ref007","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s40495-016-0050-5","article-title":"Oxidative stress under ambient and physiological oxygen tension in tissue culture.","volume":"2","author":"L Jagannathan","year":"2016","journal-title":"Curr Pharmacol Rep."},{"issue":"1","key":"ppat.1012514.ref008","first-page":"1","article-title":"Partial pressure of oxygen in the human body: a general review","volume":"9","author":"E Ortiz-Prado","year":"2019","journal-title":"Am J Blood Res"},{"issue":"15","key":"ppat.1012514.ref009","article-title":"How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen-dependent pathologies","volume":"8","author":"HM Swartz","year":"2020","journal-title":"Physiol Rep [Internet]."},{"issue":"3","key":"ppat.1012514.ref010","first-page":"385","article-title":"Human cerebral malaria. 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