{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:24:00Z","timestamp":1790738640514,"version":"4.1.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFD0900504"],"award-info":[{"award-number":["2018YFD0900504"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32130108"],"award-info":[{"award-number":["32130108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["21XD1431900"],"award-info":[{"award-number":["21XD1431900"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory","award":["311020005"],"award-info":[{"award-number":["311020005"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-47-17"],"award-info":[{"award-number":["CARS-47-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type III and type VI secretion systems (T3\/T6SS) are encoded in horizontally acquired genomic islands (GIs) that play crucial roles in evolution and virulence in bacterial pathogens. T3\/T6SS expression is subjected to tight control by the host xenogeneic silencer H-NS, but how this mechanism is counteracted remains to be illuminated. Here, we report that xenogeneic nucleoid-associated protein EnrR encoded in a GI is essential for virulence in pathogenic bacteria Edwardsiella and Salmonella. We showed that EnrR plays critical roles in T3\/T6SS expression in these bacteria. Various biochemical and genetic analyses demonstrated that EnrR binds and derepresses the promoter of esrB, the critical regulator of T3\/T6SS, to promote their expression by competing with H-NS. Additionally, EnrR targets AT-rich regions, globally modulates the expression of \u223c363 genes and is involved in various cellular processes. Crystal structures of EnrR in complex with a specific AT-rich palindromic DNA revealed a new DNA-binding mode that involves conserved HTH-mediated interactions with the major groove and contacts of its N-terminal extension to the minor groove in the symmetry-related duplex. Collectively, these data demonstrate that EnrR is a virulence activator that can antagonize H-NS, highlighting a unique mechanism by which bacterial xenogeneic regulators recognize and regulate foreign DNA.<\/jats:p>","DOI":"10.1093\/nar\/gkac180","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T15:13:06Z","timestamp":1646665986000},"page":"3777-3798","source":"Crossref","is-referenced-by-count":19,"title":["Xenogeneic nucleoid-associated EnrR thwarts H-NS silencing of bacterial virulence with unique DNA binding"],"prefix":"10.1093","volume":"50","author":[{"given":"Ruiqing","family":"Ma","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"},{"name":"Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE\/MOH, Fudan University, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabo","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-8852","authenticated-orcid":false,"given":"Jianhua","family":"Gan","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxian","family":"Qiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Bu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Shao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"},{"name":"Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai\u00a0200237,\u00a0China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"},{"name":"Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, China"},{"name":"Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai\u00a0200237,\u00a0China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-0869","authenticated-orcid":false,"given":"Qiyao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory\u00a0for Marine Science and Technology, Qingdao 266071, China"},{"name":"Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai\u00a0200237,\u00a0China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"2022042200031312000_B1","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nature06248","article-title":"Bacterial pathogenomics","volume":"449","author":"Pallen","year":"2007","journal-title":"Nature"},{"key":"2022042200031312000_B2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41586-019-1708-z","article-title":"Human gut bacteria contain acquired interbacterial defense systems","volume":"575","author":"Ross","year":"2019","journal-title":"Nature"},{"key":"2022042200031312000_B3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev-micro-102215-095301","article-title":"Xenogeneic silencing and its impact on bacterial genomes","volume":"70","author":"Singh","year":"2016","journal-title":"Annu. Rev. Microbiol."},{"key":"2022042200031312000_B4","doi-asserted-by":"crossref","first-page":"16249","DOI":"10.1038\/nmicrobiol.2016.249","article-title":"Horizontally acquired AT-rich genes in Escherichia coli cause toxicity by sequestering RNA polymerase","volume":"2","author":"Lamberte","year":"2017","journal-title":"Nat. Microbiol."},{"key":"2022042200031312000_B5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrmicro2261","article-title":"Bacterial nucleoid-associated proteins, nucleoid structure and gene expression","volume":"8","author":"Dillon","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"2022042200031312000_B6","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.csbj.2019.06.010","article-title":"Endogenous and foreign nucleoid-associated proteins of bacteria: occurrence, interactions and effects on mobile genetic elements and host's biology","volume":"17","author":"Flores-R\u00edos","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"2022042200031312000_B7","doi-asserted-by":"crossref","first-page":"fuab032","DOI":"10.1093\/femsre\/fuab032","article-title":"Hierarchy of transcription factor network in Escherichia coli K-12: H-NS-mediated silencing and anti-silencing by global regulators","volume":"45","author":"Ishihama","year":"2021","journal-title":"FEMS. Microbiol. Rev."},{"key":"2022042200031312000_B8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1126\/science.1128794","article-title":"Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella","volume":"313","author":"Navarre","year":"2006","journal-title":"Science"},{"key":"2022042200031312000_B9","doi-asserted-by":"crossref","first-page":"10690","DOI":"10.1073\/pnas.1102544108","article-title":"Structural basis for recognition of AT-rich DNA by unrelated xenogeneic silencing proteins","volume":"108","author":"Gordon","year":"2011","journal-title":"Proc. Natl. Acad. Sci. 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