{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:40:09Z","timestamp":1792276809457,"version":"4.4.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1158151"],"award-info":[{"award-number":["OPP1158151"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Key behaviours, physiologies and gene expressions in <jats:italic>Anopheles<\/jats:italic> mosquitoes impact the transmission of <jats:italic>Plasmodium<\/jats:italic>. Such mosquito factors are rhythmic to closely follow diel rhythms. Here, we set to explore the impact of the mosquito circadian rhythm on the tripartite interaction between the vector, the parasite and the midgut microbiota, and investigate how this may affect the parasite infection outcomes. We assess <jats:italic>Plasmodium falciparum<\/jats:italic> infection prevalence and intensity, as a proxy for gametocyte infectivity, in <jats:italic>Anopheles gambiae<\/jats:italic> mosquitoes that received a gametocyte-containing bloodfeed and measure the abundance of the midgut microbiota at different times of the mosquito rearing light-dark cycle. Gametocyte infectivity is also compared in mosquitoes reared and maintained under a reversed light-dark regime. The effect of the circadian clock on the infection outcome is also investigated through silencing of the <jats:italic>CLOCK<\/jats:italic> gene that is central in the regulation of animal circadian rhythms. The results reveal that the <jats:italic>A<\/jats:italic>. <jats:italic>gambiae<\/jats:italic> circadian cycle plays a key role in the intensity of infection of <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> gametocytes. We show that parasite gametocytes are more infectious during the night-time, where standard membrane feeding assays (SMFAs) at different time points in the mosquito natural circadian rhythm demonstrate that gametocytes are more infectious when ingested at midnight than midday. When mosquitoes were cultured under a reversed light\/dark regime, disrupting their natural physiological homeostasis, and infected with <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> at evening hours, the infection intensity and prevalence were significantly decreased. Similar results were obtained in mosquitoes reared under the standard light\/dark regime upon silencing of <jats:italic>CLOCK<\/jats:italic>, a key regulator of the circadian rhythm, highlighting the importance of the circadian rhythm for the mosquito vectorial capacity. At that time, the mosquito midgut microbiota load is significantly reduced, while the expression of <jats:italic>lysozyme C-1<\/jats:italic> (<jats:italic>LYSC<\/jats:italic>-1) is elevated, which is involved in both the immune response and microbiota digestion. We conclude that the tripartite interactions between the mosquito vector, the malaria parasite and the mosquito gut microbiota are finely tuned to support and maintain malaria transmission. Our data add to the knowledge framework required for designing appropriate and biologically relevant SMFA protocols.<\/jats:p>","DOI":"10.1371\/journal.pone.0278484","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T19:43:58Z","timestamp":1669923838000},"page":"e0278484","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["The circadian clock modulates Anopheles gambiae infection with Plasmodium falciparum"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3918-724X","authenticated-orcid":true,"given":"Tibebu","family":"Habtewold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Tapanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen K. G.","family":"Masters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Windbichler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George K.","family":"Christophides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"pone.0278484.ref001","volume-title":"World malaria report 2020: 20 years of global progress and challenges","author":"WHO","year":"2020"},{"issue":"7","key":"pone.0278484.ref002","doi-asserted-by":"crossref","first-page":"e1006336","DOI":"10.1371\/journal.ppat.1006336","article-title":"Developing transmission-blocking strategies for malaria control","volume":"13","author":"RE Sinden","year":"2017","journal-title":"PLoS pathogens"},{"key":"pone.0278484.ref003","doi-asserted-by":"crossref","first-page":"820650","DOI":"10.3389\/fcimb.2022.820650","article-title":"Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages","volume":"12","author":"S Yu","year":"2022","journal-title":"Frontiers in cellular and infection microbiology"},{"key":"pone.0278484.ref004","volume-title":"Guidance framework for testing of genetically modified mosquitoes","author":"M Benedict","year":"2014"},{"issue":"4","key":"pone.0278484.ref005","first-page":"474","volume":"10","author":"N Gerald","year":"2011","journal-title":"Mitosis in the human malaria parasite Plasmodium falciparum"},{"issue":"3","key":"pone.0278484.ref006","first-page":"e57909","article-title":"Qualification of standard membrane-feeding assay with Plasmodium falciparum malaria and potential improvements for future assays","volume":"8","author":"K Miura","year":"2013"},{"issue":"8","key":"pone.0278484.ref007","first-page":"e42821","article-title":"Mosquito feeding assays to determine the infectiousness of naturally infected Plasmodium falciparum gametocyte carriers","volume":"7","author":"T Bousema","year":"2012"},{"issue":"2","key":"pone.0278484.ref008","first-page":"53","article-title":"Dinglasan RRJTip. 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