{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:31:13Z","timestamp":1790357473415,"version":"4.1.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Antimicrobial resistance (AMR) poses an escalating global health threat. Potentiated sulphonamides are widely used in both veterinary and human medicine. This study aimed to investigate the\n                      <jats:italic>in vitro<\/jats:italic>\n                      adaptation of\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      strains to increasing concentrations of potentiated sulphonamides, focusing on co-selection and the genetic mechanisms of resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The MEGA-plate evolutionary model was used to expose\n                      <jats:italic>E. coli<\/jats:italic>\n                      ATCC 25922 to increased concentrations (0\u202f\u00d7\u202fto 1000\u00d7) of a potentiated sulphonamide. Clones isolated from different concentration zones were analyzed for phenotypic resistance via minimum inhibitory concentration (MIC) testing and genotypically through next-generation sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In strains adapted to 1000\u202f\u00d7\u202fpotentiated sulphonamide, MIC values significantly increased for most tested antibiotics. Mutations were identified in key folate pathway genes (\n                      <jats:italic>folP<\/jats:italic>\n                      ,\n                      <jats:italic>folA<\/jats:italic>\n                      ), as well as in efflux pump regulator genes (\n                      <jats:italic>emrR<\/jats:italic>\n                      ,\n                      <jats:italic>marR<\/jats:italic>\n                      ,\n                      <jats:italic>acrR<\/jats:italic>\n                      ,\n                      <jats:italic>mdtM<\/jats:italic>\n                      ). These genetic changes indicated activation of multiple multidrug efflux systems, including\n                      <jats:italic>acrAB-tolC<\/jats:italic>\n                      ,\n                      <jats:italic>emrAB-tolC<\/jats:italic>\n                      , and\n                      <jats:italic>mdtEF-tolC<\/jats:italic>\n                      . Mutations were also detected in genes associated with SOS response regulation (\n                      <jats:italic>recN<\/jats:italic>\n                      ,\n                      <jats:italic>recQ<\/jats:italic>\n                      ,\n                      <jats:italic>uvrB<\/jats:italic>\n                      ), suggesting stress-induced genetic adaptation.\n                      <jats:italic>In vitro<\/jats:italic>\n                      microevolutionary adaptation to potentiated sulphonamide exposure induced broad genetic changes in\n                      <jats:italic>E. coli<\/jats:italic>\n                      , potentially driving cross-resistance through co-selection. The MEGA-plate method proved to be a robust tool for tracking resistance development and dissecting complex resistance mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings underscore the need for cautious use of combination antimicrobials, as they may elicit pleiotropic resistance responses beyond their intended targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2025.1697872","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T14:47:50Z","timestamp":1764168470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Resistance evolution under potentiated sulphonamide pressure in Escherichia coli"],"prefix":"10.3389","volume":"12","author":[{"given":"\u00c1d\u00e1m","family":"Kerek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"T\u00f6r\u00f6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1bel","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Laczk\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Kardos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"B\u00e1nyai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Kaszab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Bali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1kos","family":"Jerzsele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"Doc05","DOI":"10.3205\/dgkh000290","article-title":"Antibiotic 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