{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:57:31Z","timestamp":1789243051212,"version":"build-2803163510"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":125,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009252","name":"SciLifeLab","doi-asserted-by":"publisher","award":["CTS18:80"],"award-info":[{"award-number":["CTS18:80"]}],"id":[{"id":"10.13039\/501100009252","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Shigella spp, the etiological agents of bacillary dysentery in humans, have evolved an intricate regulatory strategy to ensure fine-tuned expression of virulence genes in response to environmental stimuli. A key component in this regulation is VirF, an AraC-like transcription factor, which at the host temperature (37\u00b0C) triggers, directly or indirectly, the expression of\u00a0&amp;gt;\u00a030\u00a0virulence genes important for invasion of the intestinal epithelium. Previous work identified two different forms of VirF with distinct functions: VirF30 activates virulence gene expression, while VirF21 appears to negatively regulate virF itself. Moreover, VirF21 originates from either differential translation of the virF mRNA or from a shorter leaderless mRNA (llmRNA). Here we report that both expression of the virF21 llmRNA and the VirF21:VirF30 protein ratio are higher at 30\u00b0C than at 37\u00b0C, suggesting a possible involvement of VirF21 in minimizing virulence gene expression outside the host (30\u00b0C). Ectopic elevation of VirF21 levels at 37\u00b0C indeed suppresses Shigella\u00b4s ability to infect epithelial cells. Finally, we find that the VirF21 C-terminal portion, predicted to contain a Helix-Turn-Helix motif (HTH2), is required for the functionality of this negative virulence regulator.<\/jats:p>","DOI":"10.1093\/femsle\/fnac043","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T19:10:35Z","timestamp":1651691435000},"source":"Crossref","is-referenced-by-count":12,"title":["The VirF21:VirF30 protein ratio is affected by temperature and impacts <i>Shigella flexneri<\/i> host cell invasion"],"prefix":"10.1093","volume":"369","author":[{"given":"Eva","family":"Skovajsov\u00e1","sequence":"first","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Biochemistry and Microbiology , Uppsala University, 75123, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cC. Darwin\u201d, Istituto Pasteur Italia , Sapienza Universit\u00e0 di Roma, Rome, 00185 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-0086","authenticated-orcid":false,"given":"Gianni","family":"Prosseda","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cC. Darwin\u201d, Istituto Pasteur Italia , Sapienza Universit\u00e0 di Roma, Rome, 00185 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-0803","authenticated-orcid":false,"given":"Mikael E","family":"Sellin","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Biochemistry and Microbiology , Uppsala University, 75123, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-4000","authenticated-orcid":false,"given":"Maria Letizia","family":"Di\u00a0Martino","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Biochemistry and Microbiology , Uppsala University, 75123, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"2022062600502803000_bib1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.1365-2958.1989.tb00210.x","article-title":"A dual transcriptional activation system for the 230\u00a0kb plasmid genes coding for virulence-associated antigens of Shigella flexneri","volume":"3","author":"Adler","year":"1989","journal-title":"Mol Microbiol"},{"key":"2022062600502803000_bib2","doi-asserted-by":"crossref","first-page":"E3282","DOI":"10.1073\/pnas.1509091112","article-title":"Bioimage analysis of Shigella infection reveals targeting of colonic crypts","volume":"112","author":"Arena","year":"2015","journal-title":"Proc Natl Acad Sci"},{"key":"2022062600502803000_bib3","doi-asserted-by":"crossref","first-page":"e27226","DOI":"10.1371\/journal.pone.0027226","article-title":"A new piece of the Shigella pathogenicity puzzle: spermidine accumulation by silencing of the speG gene [corrected]","volume":"6","author":"Barbagallo","year":"2011","journal-title":"PLoS One"},{"key":"2022062600502803000_bib4","doi-asserted-by":"crossref","first-page":"6274","DOI":"10.1128\/jb.172.11.6274-6281.1990","article-title":"The two-component regulatory system ompR-envZ controls the virulence of Shigella flexneri","volume":"172","author":"Bernardini","year":"1990","journal-title":"J Bacteriol"},{"key":"2022062600502803000_bib5","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1073\/pnas.86.10.3867","article-title":"Identification of icsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin","volume":"86","author":"Bernardini","year":"1989","journal-title":"Proc Natl Acad Sci"},{"key":"2022062600502803000_bib7","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00751-19","article-title":"Shigella flexneri adherence factor expression in in vivo-like conditions","volume":"4","author":"Chanin","year":"2019","journal-title":"Msphere"},{"key":"2022062600502803000_bib8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ab.2012.08.015","article-title":"Comparison of stain-free gels with traditional immunoblot loading control methodology","volume":"430","author":"Colella","year":"2012","journal-title":"Anal Biochem"},{"key":"2022062600502803000_bib9","doi-asserted-by":"crossref","DOI":"10.1093\/femsre\/fuab020","article-title":"An update of the unceasingly growing and diverse AraC\/XylS family of transcriptional activators","volume":"45","author":"Cort\u00e9s-Avalos","year":"2021","journal-title":"FEMS Microbiol Rev"},{"key":"2022062600502803000_bib10","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1128\/jb.174.23.7606-7612.1992","article-title":"Regulation of virulence-associated plasmid genes in enteroinvasive Escherichia coli","volume":"174","author":"Dagberg","year":"1992","journal-title":"J Bacteriol"},{"key":"2022062600502803000_bib11","doi-asserted-by":"crossref","first-page":"6640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc Natl Acad Sci"},{"key":"2022062600502803000_bib6","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/B978-0-12-378630-2.00031-1","volume-title":"Bile Salts. 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