{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:52:15Z","timestamp":1789678335607,"version":"4.0.1"},"reference-count":71,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science and Innovation (MCIN)\/ Agencia Estatal de Investigaci\u00f3n (AEI)","award":["PID2019-107232RB-I00"],"award-info":[{"award-number":["PID2019-107232RB-I00"]}]},{"name":"Spanish Ministry of Science and Innovation (MCIN)\/ Agencia Estatal de Investigaci\u00f3n (AEI)","award":["PID2022-137863OB-I00"],"award-info":[{"award-number":["PID2022-137863OB-I00"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NA (co-funded grants PID2019-107232RB-I00 and PID2022-137863OB-I00)"],"award-info":[{"award-number":["NA (co-funded grants PID2019-107232RB-I00 and PID2022-137863OB-I00)"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Ministry of Science and Innovation (MCIN)\/ Agencia Estatal de Investigaci\u00f3n","award":["PRE2020-094497"],"award-info":[{"award-number":["PRE2020-094497"]}]},{"DOI":"10.13039\/100008054","name":"Fundaci\u00f3n Ram\u00f3n Areces","doi-asserted-by":"publisher","award":["Molecular Mechanisms of Malaria"],"award-info":[{"award-number":["Molecular Mechanisms of Malaria"]}],"id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Ministry of Science and Innovation (MCIN)\/ Agencia Estatal de Investigaci\u00f3n","award":["CEX2023-0001290-S"],"award-info":[{"award-number":["CEX2023-0001290-S"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["CERCA program"],"award-info":[{"award-number":["CERCA program"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    To preserve proteome homeostasis and survive at higher-than-optimal temperatures, organisms have evolved the conserved heat-shock (HS) response (HSR), characterised by increased expression of specific chaperone-encoding genes. In the human blood, malaria parasites are frequently exposed to elevated temperatures associated with host fever episodes. The protective HSR of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , the parasite that produces the vast majority of malaria clinical cases and deaths, is regulated by the transcription factor AP2-HS. Here, we systematically investigated the conditions that trigger the AP2-HS-dependent HSR and found that even mild HS conditions that do not compromise parasite viability can activate this response. As in other organisms, activation of the HSR in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    is rapid, as it was observed after a HS of only 10 min. Dihydroartemisinin (DHA), a drug that produces general proteome damage, also triggered the HSR, indicating that activation of the malarial HSR is not restricted to thermal stress. The AP2-HS-dependent HSR can be activated in all asexual blood stages, with the exception of very young rings, but not in intermediate or mature gametocyte stages. Accordingly, these gametocyte stages are highly sensitive to HS. Since mature gametocytes are the only stage that can mediate human-to-mosquito transmission, these results suggest that malaria patients with high fever may become transiently non-infectious.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014346","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:23:34Z","timestamp":1783617814000},"page":"e1014346","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterisation of the thermal and non-thermal stress conditions that activate the Plasmodium falciparum AP2-HS-dependent heat-shock response"],"prefix":"10.1371","volume":"22","author":[{"given":"Neus","family":"R\u00e0fols","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prince B.","family":"Nyarko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Chillar\u00f3n-Ad\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Tint\u00f3-Font","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0730-6582","authenticated-orcid":true,"given":"Alfred","family":"Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ppat.1014346.ref001","author":"WHO","year":"2024"},{"issue":"3","key":"ppat.1014346.ref002","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s41579-019-0306-2","article-title":"Plasmodium asexual growth and sexual development in the haematopoietic niche of the 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Gazzinelli","year":"2014","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"ppat.1014346.ref007","doi-asserted-by":"crossref","first-page":"5111","DOI":"10.1073\/pnas.88.12.5111","article-title":"Periodic and chaotic host-parasite interactions in human malaria","volume":"88","author":"D Kwiatkowski","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1014346.ref008","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1098\/rspb.1910.0075","article-title":"Some enumerative studies on malarial fever","volume":"83","author":"R Ross","year":"1910","journal-title":"Proc R Soc Lond B"},{"issue":"7","key":"ppat.1014346.ref009","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/ni.f.205","article-title":"Immunity to malaria: More questions than answers","volume":"9","author":"J Langhorne","year":"2008","journal-title":"Nat 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K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates","volume":"347","author":"J Straimer","year":"2015","journal-title":"Science"},{"issue":"6473","key":"ppat.1014346.ref035","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1126\/science.aax4735","article-title":"A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites","volume":"367","author":"J Birnbaum","year":"2020","journal-title":"Science"},{"issue":"1","key":"ppat.1014346.ref036","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1038\/s41467-018-06221-1","article-title":"Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome","volume":"9","author":"JL Bridgford","year":"2018","journal-title":"Nat Commun"},{"issue":"6220","key":"ppat.1014346.ref037","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1126\/science.1260403","article-title":"Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance","volume":"347","author":"S Mok","year":"2015","journal-title":"Science"},{"issue":"4","key":"ppat.1014346.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1002132","article-title":"Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance","volume":"13","author":"C Dogovski","year":"2015","journal-title":"PLoS Biol"},{"issue":"8","key":"ppat.1014346.ref039","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1128\/AAC.02902-14","article-title":"Flow cytometry-based analysis of artemisinin-resistant Plasmodium falciparum in the ring-stage survival assay","volume":"58","author":"C Amaratunga","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ppat.1014346.ref040","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.60058","article-title":"Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently","volume":"9","author":"HP Portugaliza","year":"2020","journal-title":"Elife"},{"issue":"10","key":"ppat.1014346.ref041","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1096\/fj.11-187401","article-title":"Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches","volume":"25","author":"EH Ekland","year":"2011","journal-title":"FASEB J"},{"issue":"1","key":"ppat.1014346.ref042","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41467-017-00572-x","article-title":"A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission","volume":"8","author":"DA Baker","year":"2017","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1014346.ref043","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41564-018-0291-7","article-title":"Revisiting the initial steps of sexual development in the malaria parasite Plasmodium 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