{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T05:54:14Z","timestamp":1786254854442,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201000513239"],"award-info":[{"award-number":["RS\u20102025\u201000513239"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201000553409"],"award-info":[{"award-number":["RS\u20102025\u201000553409"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Uropathogenic\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                    <\/jats:styled-content>\n                    (UPEC) is one of the leading causes of nosocomial infections and urinary tract infections (UTIs), capable of inducing a spectrum of conditions ranging from acute bladder cystitis to chronic pyelonephritis. The virulence arsenal of UPEC includes factors, such as curli fimbriae, hemolysin, motility elements and metallophores. Moreover, UPEC can form biofilm\u2010like communities and quiescent intracellular reservoirs within host tissues, contributing to recurrent and persistent infections. This study investigates the antibiofilm and antimicrobial activities of two halogen\u2010substituted aniline derivatives, 4\u2010bromo\u20103\u2010chloroaniline (4B3CA) and 3,5\u2010dibromoaniline (3,5\u2010DBA), against UPEC. The compounds demonstrated minimum inhibitory concentrations (MICs) of 200\u2009\u03bcg\/mL for 4B3CA and 100\u2009\u03bcg\/mL for 3,5\u2010DBA, with both exhibiting a biofilm inhibition IC50 value of 10\u2009\u03bcg\/mL. Additionally, these derivatives showed antibiofilm activity against ESKAPE pathogens. Treatment with 4B3CA and 3,5\u2010DBA led to significant downregulation of UPEC virulence\u2010 and biofilm\u2010related genes, including those involved in curli production, fimbrial adhesion, motility, iron acquisition, quiescent colony formation, and stress response. Interestingly, a mild upregulation of\n                    <jats:italic>hlyA<\/jats:italic>\n                    ,\n                    <jats:italic>csrA<\/jats:italic>\n                    and\n                    <jats:italic>uvrY<\/jats:italic>\n                    was noted, alongside a marked downregulation of the adenylate cyclase genes\n                    <jats:italic>cyaA<\/jats:italic>\n                    and\n                    <jats:italic>crp<\/jats:italic>\n                    . These findings suggest that inhibition of adenylate cyclase activity may be a primary mode of action, leading to both antimicrobial and antibiofilm effects. The presence of halogen atoms in these compounds appears to enhance their binding affinity to adenylate cyclase through stabilising halogen bond interactions. Furthermore, 3D\u2010QSAR analysis indicates that electrostatic favourability at the third and fourth positions of the aniline ring is critical for bioactivity. Finally, in silico ADMET profiling and cytotoxicity assessments using\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    <\/jats:styled-content>\n                    suggest that these aniline derivatives hold promise as therapeutic candidates, warranting further investigation.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70165","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T05:56:08Z","timestamp":1748238968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Broad\u2010Spectrum Antimicrobial and Antibiofilm Activities of Halogenated Anilines Against Uropathogenic\n                    <scp>\n                      <i>Escherichia\u00a0coli<\/i>\n                    <\/scp>\n                    and\n                    <scp>ESKAPE<\/scp>\n                    Pathogens"],"prefix":"10.1111","volume":"18","author":[{"given":"Bharath Reddy","family":"Boya","sequence":"first","affiliation":[{"name":"School of Chemical Engineering Yeungnam University  Gyeongsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Yeungnam University  Gyeongsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-1682","authenticated-orcid":false,"given":"Jintae","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering Yeungnam University  Gyeongsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065500"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CC02402D"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00351-20"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10010005"},{"issue":"1","key":"e_1_2_11_6_1","first-page":"37","article-title":"Escherichia coli Response to Exogenous Pyrophosphate and Analogs","volume":"5","author":"Biville F.","year":"2003","journal-title":"Journal of Molecular Microbiology and Biotechnology"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24031901"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.872943"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2023.127537"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02236-23"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2023.02.004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00796-12"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.123.000863"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.06.005"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2016.11.014"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.onehlt.2023.100558"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.11.3331-3334.1996"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1070363224080206"},{"key":"e_1_2_11_19_1","first-page":"114","volume-title":"Function and Regulation of Virulence\u2010Associated Siderophores in Uropathogenic Enterobacterales","author":"Heffernan J. 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