{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:04:49Z","timestamp":1784559889281,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Antibiotic contamination, particularly by tetracycline hydrochlorides, poses a severe threat to marine benthic ecosystems. This study investigates the differentiated toxicological effects and molecular defense mechanisms of the marine ciliate\n                    <jats:italic>Euplotes vannus<\/jats:italic>\n                    when exposed to three structurally similar tetracyclines: chlortetracycline hydrochloride (CTC), doxycycline hydrochloride (DOX), and tetracycline hydrochloride (TCH). Through acute (6 h) and chronic (144 h) exposure assessments, we integrated population dynamics, biochemical enzyme assays, and comparative transcriptomics. The 24-h EC\u2085\u2080 values established a toxicity gradient of CTC (4.858 mg\/L) &amp;gt; TCH (8.336 mg\/L) &amp;gt; DOX (9.023 mg\/L). Biochemical assays revealed severe lipid peroxidation across all treatments alongside distinct antioxidant enzyme activation patterns: CTC significantly induced catalase and peroxidase, whereas DOX primarily elevated superoxide dismutase activity. Transcriptomic analysis elucidated compound-specific molecular responses and survival strategies for each antibiotic. CTC exposure triggered global metabolic reprogramming, accelerating lipid and branched-chain amino acid degradation to fuel cytochrome P450-mediated detoxification and transmembrane efflux. Conversely, DOX induced profound endoplasmic reticulum stress and disrupted protein folding, necessitating the upregulation of molecular chaperones and energy systems. TCH exposure resulted in translational arrest and the global downregulation of energy metabolism, leaving\n                    <jats:italic>E. vannus<\/jats:italic>\n                    with a diminished compensatory antioxidant response despite sustaining the most severe lipid damage. These findings demonstrate that\n                    <jats:italic>E. vannus<\/jats:italic>\n                    does not deploy a uniform defense against tetracycline hydrochlorides; instead, it executes complex, compound-specific adaptive strategies involving energy reallocation, macromolecular quality control, and targeted detoxification. This study provides critical insights into the comparative ecotoxicology of marine protozoa.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1847705","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:23:53Z","timestamp":1783077833000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differentiated molecular defense strategies and survival trade-offs in the marine ciliate Euplotes vannus exposed to structurally homologous tetracyclines"],"prefix":"10.3389","volume":"17","author":[{"given":"Jialu","family":"Yu","sequence":"first","affiliation":[{"name":"School of Marine Sciences, Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.3390\/antibiotics12030440","article-title":"The impact of tetracycline pollution on the aquatic environment and removal strategies","volume":"12","author":"Amangelsin","year":"2023","journal-title":"Antibiotics"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3354\/meps010257","article-title":"The ecological role of water-column microbes in the sea","volume":"10","author":"Azam","year":"1983","journal-title":"Mar. 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Ecol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.aquatox.2005.09.009","article-title":"Ecotoxicology of human pharmaceuticals","volume":"76","author":"Fent","year":"2006","journal-title":"Aquat. Toxicol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.3390\/w16182606","article-title":"The convergence of antibiotic contamination, resistance, and climate dynamics in freshwater ecosystems","volume":"16","author":"Gomes","year":"2024","journal-title":"Water"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3354\/ame039159","article-title":"Periphytic ciliate colonization: annual cycle and responses to environmental conditions","volume":"39","author":"Gong","year":"2005","journal-title":"Aquat. Microb. 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Mol. Cell. Cardiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e123","DOI":"10.1093\/nar\/gkp596","article-title":"Transcriptome analysis by strand-specific sequencing of complementary DNA","volume":"37","author":"Parkhomchuk","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e 1260","DOI":"10.1002\/mbo3.1260","article-title":"Impact of antibiotics on the human microbiome and consequences for host health","volume":"11","author":"Patangia","year":"2022","journal-title":"Microbiol. Open"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"655059","DOI":"10.3389\/fphys.2021.655059","article-title":"Transcriptomic and metabolomic data reveal the key metabolic pathways affecting Streltzoviella insularis (Staudinger)(Lepidoptera: Cossidae) larvae during overwintering","volume":"12","author":"Pei","year":"2021","journal-title":"Front. Physiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"String tie enables improved reconstruction of a transcriptome from RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"6407","DOI":"10.1038\/onc.2008.308","article-title":"Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis","volume":"27","author":"Pinton","year":"2008","journal-title":"Oncogene"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"231","DOI":"10.15386\/mpr-1742","article-title":"Antibiotics in the environment: causes and consequences","volume":"93","author":"Polianciuc","year":"2020","journal-title":"Med. Pharm. Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ejphar.2017.10.043","article-title":"Molecular mechanism of doxorubicin-induced cardiomyopathy\u2013an update","volume":"818","author":"Renu","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1007\/s10646-013-1133-2","article-title":"Chronic exposure of river sediments to environmentally relevant levels of tetracycline affects bacterial communities but not denitrification rates","volume":"22","author":"Roose-Amsaleg","year":"2013","journal-title":"Ecotoxicology"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/S0045-6535(98)00381-6","article-title":"Tetrahymena pyriformis: a tool for toxicological studies. A review","volume":"38","author":"Sauvant","year":"1999","journal-title":"Chemosphere"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/105172397243079","article-title":"TETRATOX: Tetrahymena Pyriformis population growth impairment endpointa surrogate for fish lethality","volume":"7","author":"Schultz","year":"1997","journal-title":"Toxicology Methods"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e0306161","DOI":"10.1371\/journal.pone.0306161","article-title":"Risk assessment of antibiotic residues and resistance profile of E. coli in typical rivers of Sichuan, China","volume":"20","author":"Sha","year":"2025","journal-title":"PLoS One"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"849","DOI":"10.3390\/ijms26020849","article-title":"Comparative transcriptomic analysis reveals new insights into spawn aging in Agaricus bisporus: mitochondrial dysfunction","volume":"26","author":"Shu","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1093\/icb\/ict028","article-title":"Energy-limited tolerance to stress as a conceptual framework to integrate the effects of multiple stressors","volume":"53","author":"Sokolova","year":"2013","journal-title":"Integr. Comp. Biol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"107153","DOI":"10.1016\/j.marenvres.2025.107153","article-title":"Comparative transcriptome analysis reveals the response mechanism of the typical marine ciliate Euplotes vannus to heavy metal cadmium exposure","volume":"208","author":"Tian","year":"2025","journal-title":"Mar. Environ. Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1007\/s11802-019-4004-5","article-title":"A bioassay for the cytotoxicity of gemcitabine using the marine ciliate Euplotes vannus","volume":"18","author":"Wang","year":"2019","journal-title":"J. Ocean Univ. 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Res."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"7376","DOI":"10.1080\/21655979.2021.1974657","article-title":"Antibiotics: an overview on the environmental occurrence, toxicity, degradation, and removal methods","volume":"12","author":"Yang","year":"2021","journal-title":"Bioengineered"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"105383","DOI":"10.1016\/j.phrs.2020.105383","article-title":"Endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity may be therapeutically targeted by natural and chemical compounds: a review","volume":"164","author":"Yarmohammadi","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.011","article-title":"Cluster profiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3390\/metabo15030143","article-title":"Metabolomics\u2019 change under \u03b2-cypermethrin stress and detoxification role of CYP5011A1 in Tetrahymena thermophila","volume":"15","author":"Zhang","year":"2025","journal-title":"Meta"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"3842","DOI":"10.1021\/acs.est.7b06494","article-title":"Omics advances in ecotoxicology","volume":"52","author":"Zhang","year":"2018","journal-title":"Environ. Sci. 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