[{"oa":1,"month":"06","year":"2025","isi":1,"language":[{"iso":"eng"}],"abstract":[{"text":"Bacteria have evolved a wide range of defence strategies to protect themselves against bacterial viruses (phages). Most known bacterial antiphage defence systems target phages with DNA genomes, which raises the question of how bacteria defend against phages with RNA genomes. Bacterial toxin–antitoxin systems that cleave intracellular RNA could potentially protect bacteria against RNA phages, but this has not been explored experimentally. In this study, we investigated the role of a model toxin–antitoxin system, MazEF, in protecting Escherichia coli against two RNA phage species. When challenged with these phages, the native presence of mazEF moderately reduced population susceptibility and increased the survival of individual E. coli cells. Genomic analysis further revealed an underrepresentation of the MazF cleavage site in genomes of RNA phages infecting E. coli, indicating selection against cleavage. These results show that, in addition to other physiological roles, RNA-degrading toxin–antitoxin systems may also help defend against RNA phages.","lang":"eng"}],"publisher":"The Royal Society","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"26956E74-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","grant_number":"V00738"}],"date_updated":"2025-09-30T13:38:08Z","issue":"6","title":"A bacterial toxin-antitoxin system as a native defence element against RNA phages","author":[{"last_name":"Nikolic","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","first_name":"Nela","full_name":"Nikolic, Nela"},{"full_name":"Pleska, Maros","orcid":"0000-0001-7460-7479","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros"},{"full_name":"Bergmiller, Tobias","first_name":"Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","orcid":"0000-0001-5396-4346"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"date_published":"2025-06-11T00:00:00Z","department":[{"_id":"CaGu"}],"external_id":{"isi":["001505019800001"],"pmid":["40494395"]},"article_processing_charge":"Yes (via OA deal)","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"ec_funded":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","file":[{"checksum":"016f644ed068f8609ded306ad26dbd3f","date_updated":"2025-06-23T11:34:39Z","file_size":1850797,"file_id":"19873","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_name":"2025_BiologyLetters_Nikolic.pdf","creator":"dernst","date_created":"2025-06-23T11:34:39Z","success":1}],"file_date_updated":"2025-06-23T11:34:39Z","quality_controlled":"1","acknowledged_ssus":[{"_id":"LifeSc"}],"citation":{"chicago":"Nikolic, Nela, Maros Pleska, Tobias Bergmiller, and Calin C Guet. “A Bacterial Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” <i>Biology Letters</i>. The Royal Society, 2025. <a href=\"https://doi.org/10.1098/rsbl.2025.0080\">https://doi.org/10.1098/rsbl.2025.0080</a>.","ieee":"N. Nikolic, M. Pleska, T. Bergmiller, and C. C. Guet, “A bacterial toxin-antitoxin system as a native defence element against RNA phages,” <i>Biology Letters</i>, vol. 21, no. 6. The Royal Society, 2025.","ama":"Nikolic N, Pleska M, Bergmiller T, Guet CC. A bacterial toxin-antitoxin system as a native defence element against RNA phages. <i>Biology Letters</i>. 2025;21(6). doi:<a href=\"https://doi.org/10.1098/rsbl.2025.0080\">10.1098/rsbl.2025.0080</a>","short":"N. Nikolic, M. Pleska, T. Bergmiller, C.C. Guet, Biology Letters 21 (2025).","ista":"Nikolic N, Pleska M, Bergmiller T, Guet CC. 2025. A bacterial toxin-antitoxin system as a native defence element against RNA phages. Biology Letters. 21(6), 20250080.","apa":"Nikolic, N., Pleska, M., Bergmiller, T., &#38; Guet, C. C. (2025). A bacterial toxin-antitoxin system as a native defence element against RNA phages. <i>Biology Letters</i>. The Royal Society. <a href=\"https://doi.org/10.1098/rsbl.2025.0080\">https://doi.org/10.1098/rsbl.2025.0080</a>","mla":"Nikolic, Nela, et al. “A Bacterial Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” <i>Biology Letters</i>, vol. 21, no. 6, 20250080, The Royal Society, 2025, doi:<a href=\"https://doi.org/10.1098/rsbl.2025.0080\">10.1098/rsbl.2025.0080</a>."},"license":"https://creativecommons.org/licenses/by/4.0/","volume":21,"article_number":"20250080","article_type":"original","doi":"10.1098/rsbl.2025.0080","scopus_import":"1","ddc":["570"],"OA_type":"hybrid","has_accepted_license":"1","acknowledgement":"This work was supported by ISTFELLOW (People Program – Marie Curie Actions of the European Union’s Seventh Framework Program FP7 under REA grant agreement 291734), the FWF (Austrian Science Fund) Elise Richter Program project number V 738 and the Wellcome Trust Institutional Strategic Support Award (WT105618MA), to N.N. M.P. was a Simons Foundation Fellow of the Life Sciences Research Foundation. We are grateful to Kathrin Tomasek, Lisa Butt, Chris Estell, Alys Jepson, Franklin Nobrega, Stefano Pagliara, Remy Chait, Steve West, Vicki Gold, Josh Eaton, Ivana Gudelj and Rob Beardmore for useful discussions and technical support, as well as to Robin Wright, Christian Fitch and Ben Temperton for sharing equipment. We thank Laurence Van Melderen for sharing the strains. We acknowledge the IST Austria Lab Support Facility, LSI Technical Services Team at the University of Exeter and the Translational Research Exchange @ Exeter (TREE) network. N.N. is grateful to Fabrice Gielen for his support.","day":"11","intvolume":"        21","OA_place":"publisher","publication_status":"published","publication_identifier":{"issn":["1744-9561"],"eissn":["1744-957X"]},"_id":"19857","publication":"Biology Letters","status":"public","oa_version":"Published Version","type":"journal_article","date_created":"2025-06-22T22:02:06Z","corr_author":"1","pmid":1},{"oa_version":"Published Version","publication":"BMC Research Notes","status":"public","type":"journal_article","date_created":"2022-08-01T09:04:27Z","pmid":1,"corr_author":"1","related_material":{"link":[{"url":"https://doi.org/10.1186/s13104-022-06152-7","relation":"erratum"}]},"scopus_import":"1","has_accepted_license":"1","acknowledgement":"We acknowledge the Max Perutz Labs FACS Facility together with Thomas Sauer. NN is grateful to Călin C. Guet for his support.\r\nThis work was funded by the Elise Richter grant V738 of the Austrian Science Fund (FWF), and the FWF Lise Meitner grant M1697, to NN; and by the FWF grant P22249, FWF Special Research Program RNA-REG F43 (subproject F4316), and FWF doctoral program RNA Biology (W1207), to IM. Open access funding provided by the Austrian Science Fund.","ddc":["570"],"publication_status":"published","intvolume":"        15","day":"13","_id":"11713","publication_identifier":{"issn":["1756-0500"]},"volume":15,"citation":{"mla":"Nikolic, Nela, et al. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” <i>BMC Research Notes</i>, vol. 15, 173, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13104-022-06061-9\">10.1186/s13104-022-06061-9</a>.","ama":"Nikolic N, Sauert M, Albanese TG, Moll I. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. <i>BMC Research Notes</i>. 2022;15. doi:<a href=\"https://doi.org/10.1186/s13104-022-06061-9\">10.1186/s13104-022-06061-9</a>","apa":"Nikolic, N., Sauert, M., Albanese, T. G., &#38; Moll, I. (2022). Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. <i>BMC Research Notes</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13104-022-06061-9\">https://doi.org/10.1186/s13104-022-06061-9</a>","ista":"Nikolic N, Sauert M, Albanese TG, Moll I. 2022. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. BMC Research Notes. 15, 173.","short":"N. Nikolic, M. Sauert, T.G. Albanese, I. Moll, BMC Research Notes 15 (2022).","chicago":"Nikolic, Nela, Martina Sauert, Tanino G. Albanese, and Isabella Moll. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” <i>BMC Research Notes</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13104-022-06061-9\">https://doi.org/10.1186/s13104-022-06061-9</a>.","ieee":"N. Nikolic, M. Sauert, T. G. Albanese, and I. Moll, “Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli,” <i>BMC Research Notes</i>, vol. 15. Springer Nature, 2022."},"article_type":"letter_note","article_number":"173","doi":"10.1186/s13104-022-06061-9","file":[{"access_level":"open_access","creator":"dernst","file_name":"2022_BMCResearchNotes_Nikolic.pdf","date_created":"2022-08-01T09:24:42Z","success":1,"checksum":"008156e5340e9789f0f6d82bde4d347a","file_size":1545310,"date_updated":"2022-08-01T09:24:42Z","file_id":"11714","content_type":"application/pdf","relation":"main_file"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2022-08-01T09:24:42Z","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"title":"Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli","keyword":["General Biochemistry","Genetics and Molecular Biology","General Medicine"],"date_updated":"2025-04-14T09:24:53Z","date_published":"2022-05-13T00:00:00Z","author":[{"full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","first_name":"Nela","last_name":"Nikolic","orcid":"0000-0001-9068-6090"},{"last_name":"Sauert","first_name":"Martina","full_name":"Sauert, Martina"},{"first_name":"Tanino G.","last_name":"Albanese","full_name":"Albanese, Tanino G."},{"full_name":"Moll, Isabella","last_name":"Moll","first_name":"Isabella"}],"department":[{"_id":"CaGu"}],"article_processing_charge":"No","external_id":{"pmid":["35562780"]},"abstract":[{"lang":"eng","text":"Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli. The MazEF system has been used in various biotechnology and synthetic biology applications. In this study, we infer how ectopic mazF overexpression affects production of heterologous proteins. To this end, we quantified the levels of fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the 5′-untranslated region of these reporter mRNAs under the same conditions by comparing expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless mRNA).\r\nResults: Flow cytometry analysis indicates that during mazF overexpression, fluorescent proteins are translated from the canonical as well as leaderless mRNAs. Our analysis further indicates that longer mazF overexpression generally increases the concentration of fluorescent proteins translated from ACA-less mRNAs, however it also substantially increases bacterial population heterogeneity. Finally, our results suggest that the strength and duration of mazF overexpression should be optimized for each experimental setup, to maximize the heterologous protein production and minimize the amount of phenotypic heterogeneity in bacterial populations, which is unfavorable in biotechnological processes."}],"publisher":"Springer Nature","project":[{"_id":"26956E74-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","grant_number":"V00738"}],"oa":1,"year":"2022","month":"05","language":[{"iso":"eng"}]}]