{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:41:24Z","timestamp":1790462484553,"version":"4.1.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI128164"],"award-info":[{"award-number":["AI128164"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI140740"],"award-info":[{"award-number":["AI140740"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Enteric infections caused by the gram-negative bacteria enterotoxigenic <jats:italic>Escherichia coli<\/jats:italic> (ETEC), <jats:italic>Vibrio cholerae<\/jats:italic>, <jats:italic>Shigella flexneri<\/jats:italic>, and <jats:italic>Salmonella enterica<\/jats:italic> are among the most common and affect billions of people each year. These bacteria control expression of virulence factors using a network of transcriptional regulators, some of which are modulated by small molecules as has been shown for ToxT, an AraC family member from <jats:italic>V. cholerae<\/jats:italic>. In ETEC the expression of many types of adhesive pili is dependent upon the AraC family member Rns. We present here the 3\u00a0\u00c5 crystal structure of Rns and show it closely resembles ToxT. Rns crystallized as a dimer via an interface similar to that observed in other dimeric AraC\u2019s.\u00a0Furthermore, the structure of\u00a0Rns revealed the presence of a ligand, decanoic acid, that inhibits its activity in a manner similar to the fatty acid mediated inhibition observed for ToxT and the <jats:italic>S. enterica<\/jats:italic> homologue HilD. Together, these results support our hypothesis that fatty acids regulate virulence controlling AraC family members in a common manner across a number of enteric pathogens. Furthermore, for the first time this work identifies a small molecule capable of inhibiting the ETEC Rns regulon, providing a basis for development of therapeutics against this deadly human pathogen.<\/jats:p>","DOI":"10.1038\/s41598-021-95123-2","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T10:03:01Z","timestamp":1627898581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Structure of the master regulator Rns reveals an inhibitor of enterotoxigenic\u00a0Escherichia coli virulence regulons"],"prefix":"10.1038","volume":"11","author":[{"given":"Charles R.","family":"Midgett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacey Marie","family":"Talbot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Munson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Jon","family":"Kull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"95123_CR1","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/S1473-3099(17)30276-1","volume":"17","author":"C Troeger","year":"2017","unstructured":"Troeger, C. et al. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect. Dis. 17, 909\u2013948 (2017).","journal-title":"Lancet Infect. Dis."},{"key":"95123_CR2","first-page":"98","volume":"74","author":"World Health Organization","year":"1999","unstructured":"World Health Organization. New frontiers in the development of vaccines against enterotoxinogenic (ETEC) and enterohaemorrhagic (EHEC) E. coli infections. Part I. Wkly. Epidemiol. Rec. 74, 98\u2013101 (1999).","journal-title":"Wkly. Epidemiol. Rec."},{"key":"95123_CR3","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/S1473-3099(18)30475-4","volume":"18","author":"IA Khalil","year":"2018","unstructured":"Khalil, I. A. et al. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: The Global Burden of Disease Study 1990\u20132016. Lancet Infect. Dis. 18, 1229\u20131240 (2018).","journal-title":"Lancet Infect. Dis."},{"key":"95123_CR4","doi-asserted-by":"publisher","first-page":"4","DOI":"10.7205\/MILMED-D-17-00064","volume":"182","author":"CK Porter","year":"2017","unstructured":"Porter, C. K., Olson, S., Hall, A. & Riddle, M. S. Travelers\u2019 diarrhea: An update on the incidence, etiology, and risk in military deployments and similar travel populations. Mil. Med. 182, 4\u201310 (2017).","journal-title":"Mil. Med."},{"key":"95123_CR5","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1093\/jtm\/tax003","volume":"24","author":"ZD Jiang","year":"2017","unstructured":"Jiang, Z. D. & DuPont, H. L. Etiology of travellers\u2019 diarrhea. J. Travel Med. 24, S13\u2013S16 (2017).","journal-title":"J. Travel Med."},{"key":"95123_CR6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0140-6736(78)91921-9","volume":"2","author":"TK Satterwhite","year":"1978","unstructured":"Satterwhite, T. K., Evans, D. G., DuPont, H. L. & Evans, D. J. Role of Escherichia coli colonisation factor antigen in acute diarrhoea. The Lancet 2, 181\u2013184 (1978).","journal-title":"The Lancet"},{"key":"95123_CR7","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1128\/iai.19.3.883-888.1978","volume":"19","author":"DG Evans","year":"1978","unstructured":"Evans, D. G., Satterwhite, T. K., Evans, D. J. & DuPont, H. L. Differences in serological responses and excretion patterns of volunteers challenged with enterotoxigenic Escherichia coli with and without the colonization factor antigen. Infect. Immun. 19, 883\u2013888 (1978).","journal-title":"Infect. Immun."},{"key":"95123_CR8","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1574-6968.2006.00401.x","volume":"263","author":"SM Turner","year":"2006","unstructured":"Turner, S. M., Scott-Tucker, A., Cooper, L. M. & Henderson, I. R. Weapons of mass destruction: Virulence factors of the global killer enterotoxigenic Escherichia coli. FEMS Microbiol. Lett. 263, 10\u201320 (2006).","journal-title":"FEMS Microbiol. Lett."},{"key":"95123_CR9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11908-019-0665-x","volume":"21","author":"JM Fleckenstein","year":"2019","unstructured":"Fleckenstein, J. M. & Kuhlmann, F. M. Enterotoxigenic Escherichia coli infections. Curr. Infect. Dis. Rep. 21, 9\u20139 (2019).","journal-title":"Curr. Infect. Dis. Rep."},{"key":"95123_CR10","first-page":"15","volume":"21","author":"EC Boedeker","year":"2005","unstructured":"Boedeker, E. C. Vaccines for enterotoxigenic Escherichia coli: Current status. Curr. Opin. Gastroenterol. 21, 15\u201319 (2005).","journal-title":"Curr. Opin. Gastroenterol."},{"key":"95123_CR11","doi-asserted-by":"publisher","first-page":"e0007037","DOI":"10.1371\/journal.pntd.0007037","volume":"13","author":"RM Vidal","year":"2019","unstructured":"Vidal, R. M. et al. Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS). PLoS Negl. Trop. Dis. 13, e0007037 (2019).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"95123_CR12","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/S1473-3099(19)30571-7","volume":"20","author":"F Qadri","year":"2020","unstructured":"Qadri, F. et al. Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: A double-blind, randomised, placebo-controlled phase 1\/2 trial. Lancet Infect. Dis. 20, 208\u2013219 (2020).","journal-title":"Lancet Infect. Dis."},{"key":"95123_CR13","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1016\/j.idc.2019.05.007","volume":"33","author":"S Shakoor","year":"2019","unstructured":"Shakoor, S., Platts-Mills, J. A. & Hasan, R. Antibiotic-resistant enteric infections. Infect. Dis. Clin. N. Am. 33, 1105\u20131123 (2019).","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"95123_CR14","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1128\/iai.58.4.874-878.1990","volume":"58","author":"J Caron","year":"1990","unstructured":"Caron, J. & Scott, J. R. A rns-like regulatory gene for colonization factor antigen I (CFA\/I) that controls expression of CFA\/I pilin. Infect. Immun. 58, 874\u2013878 (1990).","journal-title":"Infect. Immun."},{"key":"95123_CR15","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1073\/pnas.86.3.963","volume":"86","author":"J Caron","year":"1989","unstructured":"Caron, J., Coffield, L. M. & Scott, J. R. A plasmid-encoded regulatory gene, rns, required for expression of the CS1 and CS2 adhesins of enterotoxigenic Escherichia coli. Proc. Natl. Acad. Sci. 86, 963\u2013967 (1989).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"95123_CR16","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/1471-2180-8-180","volume":"8","author":"MD Bodero","year":"2008","unstructured":"Bodero, M. D., Harden, E. A. & Munson, G. P. Transcriptional regulation of subclass 5b fimbriae. BMC Microbiol. 8, 180\u2013210 (2008).","journal-title":"BMC Microbiol."},{"key":"95123_CR17","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/j.1574-6968.1991.tb04487.x","volume":"83","author":"LA de Haan","year":"1991","unstructured":"de Haan, L. A., Willshaw, G. A., van der Zeijst, B. A. & Gaastra, W. The nucleotide sequence of a regulatory gene present on a plasmid in an enterotoxigenic Escherichia coli strain of serotype O167:H5. FEMS Microbiol. Lett. 83, 341\u2013346 (1991).","journal-title":"FEMS Microbiol. Lett."},{"key":"95123_CR18","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s12026-013-8453-4","volume":"57","author":"GP Munson","year":"2013","unstructured":"Munson, G. P. Virulence regulons of enterotoxigenic Escherichia coli. Immunol. Res. 57, 229\u2013236 (2013).","journal-title":"Immunol. Res."},{"key":"95123_CR19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.3390\/genes7120120","volume":"7","author":"MDR Bodero","year":"2016","unstructured":"Bodero, M. D. R. & Munson, G. P. The virulence regulator Rns activates the expression of CS14 pili. Genes (Basel) 7, 120 (2016).","journal-title":"Genes (Basel)"},{"key":"95123_CR20","first-page":"255","volume":"56","author":"GA Willshaw","year":"1990","unstructured":"Willshaw, G. A., McConnell, M. M., Smith, H. R. & Rowe, B. Structural and regulatory genes for coli surface associated antigen 4 (CS4) are encoded by separate plasmids in enterotoxigenic Escherichia coli strains of serotype 0.25.H42. FEMS Microbiol. Lett. 56, 255\u2013260 (1990).","journal-title":"FEMS Microbiol. Lett."},{"key":"95123_CR21","first-page":"393","volume":"61","author":"M-T Gallegos","year":"1997","unstructured":"Gallegos, M.-T., Schleif, R., Bairoch, A., Hofmann, K. & Ramos, J. L. Arac\/XylS family of transcriptional regulators. Microbiol. Mol. Biol. Rev. 61, 393\u2013410 (1997).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"95123_CR22","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/0264-410X(93)90021-O","volume":"11","author":"HM Grewal","year":"1993","unstructured":"Grewal, H. M., Gaastra, W., Svennerholm, A.-M. & R\u00f6li, J. Induction of colonization factor antigen I (CFA\/I) and coli surface antigen 4 (CS4) of enterotoxigenic Escherichia coli: Relevance for vaccine production. Vaccine 11, 221\u2013226 (1993).","journal-title":"Vaccine"},{"key":"95123_CR23","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1128\/JB.181.7.2110-2117.1999","volume":"181","author":"GP Munson","year":"1999","unstructured":"Munson, G. P. & Scott, J. R. Binding site recognition by Rns, a virulence regulator in the AraC family. J. Bacteriol. 181, 2110\u20132117 (1999).","journal-title":"J. Bacteriol."},{"key":"95123_CR24","doi-asserted-by":"publisher","first-page":"6974","DOI":"10.1128\/jb.174.21.6974-6980.1992","volume":"174","author":"DE Higgins","year":"1992","unstructured":"Higgins, D. E., Nazareno, E. & DiRita, V. J. The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC family of transcriptional activators. J. Bacteriol. 174, 6974\u20136980 (1992).","journal-title":"J. Bacteriol."},{"key":"95123_CR25","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1099\/mic.0.038521-0","volume":"156","author":"V Mahon","year":"2010","unstructured":"Mahon, V., Smyth, C. J. & Smith, S. G. J. Mutagenesis of the Rns regulator of enterotoxigenic Escherichia coli reveals roles for a linker sequence and two helix-turn-helix motifs. Microbiology (Reading) 156, 2796\u20132806 (2010).","journal-title":"Microbiology (Reading)"},{"key":"95123_CR26","doi-asserted-by":"publisher","first-page":"5403","DOI":"10.1073\/pnas.88.12.5403","volume":"88","author":"VJ DiRita","year":"1991","unstructured":"DiRita, V. J., Parsot, C., Jander, G. & Mekalanos, J. J. Regulatory cascade controls virulence in Vibrio cholerae. Proc. Natl. Acad. Sci. 88, 5403\u20135407 (1991).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"95123_CR27","doi-asserted-by":"publisher","first-page":"2860","DOI":"10.1073\/pnas.0915021107","volume":"107","author":"MJ Lowden","year":"2010","unstructured":"Lowden, M. J. et al. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes. Proc. Natl. Acad. Sci. U.S.A. 107, 2860\u20132865 (2010).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"95123_CR28","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1128\/IAI.01435-06","volume":"75","author":"A Chatterjee","year":"2007","unstructured":"Chatterjee, A., Dutta, P. K. & Chowdhury, R. Effect of fatty acids and cholesterol present in bile on expression of virulence factors and motility of Vibrio cholerae. Infect. Immun. 75, 1946\u20131953 (2007).","journal-title":"Infect. Immun."},{"key":"95123_CR29","doi-asserted-by":"publisher","first-page":"11593","DOI":"10.1021\/bi001262g","volume":"39","author":"N LaRonde-LeBlanc","year":"2000","unstructured":"LaRonde-LeBlanc, N. & Wolberger, C. Characterization of the oligomeric states of wild type and mutant AraC. Biochemistry 39, 11593\u201311601 (2000).","journal-title":"Biochemistry"},{"key":"95123_CR30","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1126\/science.276.5311.421","volume":"276","author":"SM Soisson","year":"1997","unstructured":"Soisson, S. M., MacDougall-Shackleton, B., Schleif, R. & Wolberger, C. Structural basis for ligand-regulated oligomerization of AraC. Science 276, 421\u2013425 (1997).","journal-title":"Science"},{"key":"95123_CR31","doi-asserted-by":"publisher","first-page":"e0136533","DOI":"10.1371\/journal.pone.0136533","volume":"10","author":"M Shrestha","year":"2015","unstructured":"Shrestha, M., Xiao, Y., Robinson, H. & Schubot, F. D. Structural analysis of the regulatory domain of ExsA, a key transcriptional regulator of the type three secretion system in Pseudomonas aeruginosa. PLoS ONE 10, e0136533 (2015).","journal-title":"PLoS ONE"},{"key":"95123_CR32","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s10709-007-9185-y","volume":"133","author":"JA Ibarra","year":"2008","unstructured":"Ibarra, J. A., Perez-Rueda, E., Segovia, L. & Puente, J. L. The DNA-binding domain as a functional indicator: The case of the AraC\/XylS family of transcription factors. Genetica 133, 65\u201376 (2008).","journal-title":"Genetica"},{"key":"95123_CR33","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.pep.2005.01.016","volume":"41","author":"FW Studier","year":"2005","unstructured":"Studier, F. W. Protein production by auto-induction in high-density shaking cultures. Protein Expr. Purif. 41, 207\u2013234 (2005).","journal-title":"Protein Expr. Purif."},{"key":"95123_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 1\u20138 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"95123_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: A comprehensive python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 1\u20139 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"95123_CR36","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: Model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"95123_CR37","first-page":"1605","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF chimera\u2014A visualization system for exploratory research and analysis. J. Comp. Biol. 25, 1605\u20131612 (2004).","journal-title":"J. Comp. Biol."},{"key":"95123_CR38","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/pro.3235","volume":"27","author":"TD Goddard","year":"2017","unstructured":"Goddard, T. D. et al. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 27, 14\u201325 (2017).","journal-title":"Protein Sci."},{"key":"95123_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1107\/S0021889807021206","volume":"40","author":"AJ McCoy","year":"2007","unstructured":"McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Cryst. 40, 1\u201317 (2007).","journal-title":"J. Appl. Cryst."},{"key":"95123_CR40","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1038\/nprot.2007.321","volume":"2","author":"FH Niesen","year":"2007","unstructured":"Niesen, F. H., Berglund, H. & Vedadi, M. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2, 2212\u20132221 (2007).","journal-title":"Nat. Protoc."},{"key":"95123_CR41","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/mmi.13699","volume":"105","author":"CR Midgett","year":"2017","unstructured":"Midgett, C. R. et al. Bile salts and alkaline pH reciprocally modulate the interaction between the periplasmic domains of Vibrio cholerae ToxR and ToxS. Mol. Microbiol. 105, 258\u2013272 (2017).","journal-title":"Mol. Microbiol."},{"key":"95123_CR42","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1128\/JB.01714-06","volume":"189","author":"MD Bodero","year":"2007","unstructured":"Bodero, M. D., Pilonieta, M. C. & Munson, G. P. Repression of the inner membrane lipoprotein NlpA by Rns in enterotoxigenic Escherichia coli. J. Bacteriol. 189, 1627\u20131632 (2007).","journal-title":"J. Bacteriol."},{"key":"95123_CR43","doi-asserted-by":"publisher","first-page":"6384","DOI":"10.1128\/JB.183.21.6384-6393.2001","volume":"183","author":"A Haldimann","year":"2001","unstructured":"Haldimann, A. & Wanner, B. L. Conditional-replication, integration, excision, and retrieval plasmid-host systems for gene structure-function studies of bacteria. J. Bacteriol. 183, 6384\u20136393 (2001).","journal-title":"J. Bacteriol."},{"key":"95123_CR44","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1128\/JB.01705-07","volume":"190","author":"GN Basturea","year":"2008","unstructured":"Basturea, G. N., Bodero, M. D., Moreno, M. E. & Munson, G. P. Residues near the amino terminus of Rns are essential for positive autoregulation and DNA binding. J. Bacteriol. 190, 2279\u20132285 (2008).","journal-title":"J. Bacteriol."},{"key":"95123_CR45","doi-asserted-by":"publisher","first-page":"5060","DOI":"10.1128\/JB.00131-07","volume":"189","author":"MC Pilonieta","year":"2007","unstructured":"Pilonieta, M. C., Bodero, M. D. & Munson, G. P. CfaD-dependent expression of a novel extracytoplasmic protein from enterotoxigenic Escherichia coli. J. Bacteriol. 189, 5060\u20135067 (2007).","journal-title":"J. Bacteriol."},{"key":"95123_CR46","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/0022-2836(76)90119-4","volume":"104","author":"MJ Casadaban","year":"1976","unstructured":"Casadaban, M. J. Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu. J. Mol. Biol. 104, 541\u2013555 (1976).","journal-title":"J. Mol. Biol."},{"key":"95123_CR47","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1073\/pnas.120163297","volume":"97","author":"KA Datsenko","year":"2000","unstructured":"Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. 97, 6640\u20136645 (2000).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"95123_CR48","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3389\/fmicb.2020.01374","volume":"11","author":"ZP Rivas","year":"2020","unstructured":"Rivas, Z. P. et al. CexE Is a coat protein and virulence factor of diarrheagenic pathogens. Front. Microbiol. 11, 1374 (2020).","journal-title":"Front. Microbiol."},{"key":"95123_CR49","volume-title":"Experiments in Molecular Genetics","author":"JH Miller","year":"1972","unstructured":"Miller, J. H. Experiments in Molecular Genetics (Cold Spring Harbor Laboratory Press, 1972)."},{"key":"95123_CR50","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1128\/iai.5.4.622-624.1972","volume":"5","author":"FJ Skerman","year":"1972","unstructured":"Skerman, F. J., Formal, S. B. & Falkow, S. Plasmid-associated enterotoxin production in a strain of Escherichia coli isolated from humans. Infect. Immun. 5, 622\u2013624 (1972).","journal-title":"Infect. Immun."},{"key":"95123_CR51","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1006\/mpat.1995.0034","volume":"18","author":"I Adlerberth","year":"1995","unstructured":"Adlerberth, I. et al. Adhesins of Escherichia coli associated with extra-intestinal pathogenicity confer binding to colonic epithelial cells. Microb. Pathog. 18, 373\u2013385 (1995).","journal-title":"Microb. Pathog."},{"key":"95123_CR52","doi-asserted-by":"publisher","first-page":"6460","DOI":"10.1128\/jb.173.20.6460-6468.1991","volume":"173","author":"DW Frank","year":"1991","unstructured":"Frank, D. W. & Iglewski, B. H. Cloning and sequence analysis of a trans-regulatory locus required for exoenzyme S synthesis in Pseudomonas aeruginosa. J. Bacteriol. 173, 6460\u20136468 (1991).","journal-title":"J. Bacteriol."},{"key":"95123_CR53","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1126\/science.2237403","volume":"250","author":"RB Lobell","year":"1990","unstructured":"Lobell, R. B. & Schleif, R. F. DNA looping and unlooping by AraC protein. Science 250, 528\u2013532 (1990).","journal-title":"Science"},{"key":"95123_CR54","doi-asserted-by":"publisher","first-page":"e1008776","DOI":"10.1371\/journal.ppat.1008776","volume":"16","author":"L Belmont-Monroy","year":"2020","unstructured":"Belmont-Monroy, L. et al. Characterization of a novel AraC\/XylS-regulated family of N-acyltransferases in pathogens of the order Enterobacterales. PLoS Pathog. 16, e1008776 (2020).","journal-title":"PLoS Pathog."},{"key":"95123_CR55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63762","author":"C Icke","year":"2021","unstructured":"Icke, C. et al. Glycine acylation and trafficking of a new class of bacterial lipoprotein by a composite secretion system. Elife. https:\/\/doi.org\/10.7554\/eLife.63762 (2021).","journal-title":"Elife"},{"key":"95123_CR56","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1046\/j.1365-2958.2000.01957.x","volume":"36","author":"GP Munson","year":"2000","unstructured":"Munson, G. P. & Scott, J. R. Rns, a virulence regulator within the AraC family, requires binding sites upstream and downstream of its own promoter to function as an activator. Mol. Microbiol. 36, 1391\u20131402 (2000).","journal-title":"Mol. Microbiol."},{"key":"95123_CR57","doi-asserted-by":"publisher","first-page":"4691","DOI":"10.1128\/jb.176.15.4691-4699.1994","volume":"176","author":"JP Nataro","year":"1994","unstructured":"Nataro, J. P., Yikang, D., Yingkang, D. & Walker, K. AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli. J. Bacteriol. 176, 4691\u20134699 (1994).","journal-title":"J. Bacteriol."},{"key":"95123_CR58","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1002\/jsfa.10870","volume":"101","author":"A Deen","year":"2021","unstructured":"Deen, A. et al. Chemical composition and health benefits of coconut oil: An overview. J. Sci. Food Agric. 101, 2182\u20132193 (2021).","journal-title":"J. Sci. Food Agric."},{"key":"95123_CR59","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3168\/jds.S0022-0302(02)74079-4","volume":"85","author":"RG Jensen","year":"2002","unstructured":"Jensen, R. G. The composition of bovine milk lipids: January 1995 to December 2000. J. Dairy Sci. 85, 295\u2013350 (2002).","journal-title":"J. Dairy Sci."},{"key":"95123_CR60","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4103\/japtr.JAPTR_91_20","volume":"12","author":"M Nainggolan","year":"2021","unstructured":"Nainggolan, M. & Sinaga, A. G. S. Characteristics of fatty acid composition and minor constituents of red palm olein and palm kernel oil combination. J. Adv. Pharm. Technol. Res. 12, 22\u201326 (2021).","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"95123_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/01.ASW.0000557832.86268.64","volume":"32","author":"AQ Alves","year":"2019","unstructured":"Alves, A. Q. et al. The fatty acid composition of vegetable oils and their potential use in wound care. Adv. Skin Wound Care 32, 1\u20138 (2019).","journal-title":"Adv. Skin Wound Care"},{"key":"95123_CR62","doi-asserted-by":"publisher","first-page":"299S","DOI":"10.1093\/ajcn\/55.1.299s","volume":"55","author":"WF Caspary","year":"1992","unstructured":"Caspary, W. F. Physiology and pathophysiology of intestinal absorption. Am. J. Clin. Nutr. 55, 299S-308S (1992).","journal-title":"Am. J. Clin. Nutr."},{"key":"95123_CR63","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1172\/JCI106561","volume":"50","author":"JG Banwell","year":"1971","unstructured":"Banwell, J. G., Gorbach, S. L., Pierce, N. F., Mitra, R. & Mondal, A. Acute undifferentiated human diarrhea in the tropics: II. Alterations in intestinal fluid and electrolyte movements. J. Clin. Investig. 50, 890\u2013900 (1971).","journal-title":"J. Clin. Investig."},{"key":"95123_CR64","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1128\/JB.01214-08","volume":"191","author":"DG Davies","year":"2009","unstructured":"Davies, D. G. & Marques, C. N. H. A fatty acid messenger is responsible for inducing dispersion in microbial biofilms. J. Bacteriol. 191, 1393\u20131403 (2009).","journal-title":"J. Bacteriol."},{"key":"95123_CR65","doi-asserted-by":"publisher","first-page":"816","DOI":"10.3390\/ph8040816","volume":"8","author":"CNH Marques","year":"2015","unstructured":"Marques, C. N. H., Davies, D. G. & Sauer, K. Control of biofilms with the fatty acid signaling molecule cis-2-decenoic acid. Pharmaceuticals (Basel) 8, 816\u2013835 (2015).","journal-title":"Pharmaceuticals (Basel)"},{"key":"95123_CR66","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s42003-019-0686-x","volume":"2","author":"JT Cruite","year":"2019","unstructured":"Cruite, J. T. et al. Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile. Commun. Biol. 2, 440 (2019).","journal-title":"Commun. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95123-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95123-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95123-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,5]],"date-time":"2023-02-05T09:08:34Z","timestamp":1675588114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95123-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,2]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["95123"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-95123-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,2]]},"assertion":[{"value":"7 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15663"}}