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The authors have not disclosed any funding."},{"name":"Badr University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The emergence of antimicrobial resistance in bacterial pathogens is a growing concern worldwide due to its impact on the treatment of bacterial infections. The \"Trojan Horse\" strategy has been proposed as a potential solution to overcome drug resistance caused by permeability issues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of our research was to investigate the bactericidal activity and mechanism of action of the \"Trojan Horse\" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin against the antibiotic-resistant Escherichia coli strain OQ866153.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Enterobactin, a mixed ligand of\n                      <jats:italic>E. coli<\/jats:italic>\n                      OQ866153, was conjugated with Ciprofloxacin and Fosfomycin individually to aid active absorption via specific enterobactin binding proteins (\n                      <jats:italic>FepABCDG<\/jats:italic>\n                      ). The effectiveness of the conjugates was assessed by measuring their bactericidal activity against\n                      <jats:italic>E. coli<\/jats:italic>\n                      OQ866153, as well as their ability to inhibit DNA\n                      <jats:italic>gyrase<\/jats:italic>\n                      enzyme and biofilm formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The Fe\n                      <jats:sup>+3<\/jats:sup>\n                      -enterobactin-Ciprofloxacin conjugate effectively inhibited the DNA\n                      <jats:italic>gyr<\/jats:italic>\n                      ase enzyme (Docking score\u2009=\u2009-8.597\u00a0kcal\/mol) and resulted in a lower concentration (25\u00a0\u03bcg\/ml) required to eliminate supercoiled DNA plasmids compared to the parent drug (35\u00a0\u03bcg\/ml; Docking score\u2009=\u2009-6.264\u00a0kcal\/mol). The Fe\n                      <jats:sup>+3<\/jats:sup>\n                      -Enterobactin-Fosfomycin conjugate showed a higher inhibition percentage (100%) of biofilm formation compared to Fosfomycin (21.58%) at a concentration of 2\u00a0mg\/ml, with docking scores of -5.481 and -3.756\u00a0kcal\/mol against UDP-N acetylglucosamine 1-carboxyvinyltransferase\n                      <jats:italic>MurA<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The findings of this study suggest that the \"Trojan Horse\" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin can effectively overcome permeability issues caused by efflux proteins and enhance the bactericidal activity of these drugs against antibiotic-resistant strains of\n                      <jats:italic>E. coli<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-024-03248-x","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T07:06:09Z","timestamp":1711091169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In vitro and in silico studies of enterobactin-inspired Ciprofloxacin and Fosfomycin first generation conjugates on the antibiotic resistant E. coli OQ866153"],"prefix":"10.1186","volume":"24","author":[{"given":"Mohamed T.","family":"Khazaal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H. 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