{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:02:16Z","timestamp":1779778936357,"version":"3.53.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The emergence of cefiderocol resistance in\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      poses a threat to this last line antibiotic against carbapenem-resistant infections. This study aimed to induce and characterize the mechanisms of cefiderocol resistance\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cefiderocol resistance was induced in four clinical\n                      <jats:italic>E. coli<\/jats:italic>\n                      strains (carrying\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-5<\/jats:sub>\n                      ,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      ,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>OXA-48<\/jats:sub>\n                      ,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>IMP-4<\/jats:sub>\n                      ) and ATCC 25922 via serial passaging in increasing drug concentrations. Resistant strains were subjected to whole-genome sequencing (WGS) and RNA sequencing (RNA-Seq) to identify genetic determinants. Phenotypic changes were assessed through growth kinetics, biofilm formation assays, and transmission electron microscopy (TEM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Resistance developed in all strains within 4\u201359\u202fdays. Small-colony-variant (SCV) emerged in all strains except K66460L (carrying\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-5<\/jats:sub>\n                      ), which developed resistance within only 4\u202fdays. The resistant strains showed reduced biofilm production and impaired growth kinetics. WGS revealed mutations in genes related to iron transport, membrane function, and metabolic pathways. RNA-Seq confirmed altered expression of iron transport genes. TEM showed that resistant strains had an increased cell wall diameter. In addition, results of our study confirm the role of serine and metallo-beta-lactamase enzymes in cefiderocol resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Cefiderocol resistance can be rapidly selected in\n                      <jats:italic>E. coli<\/jats:italic>\n                      through diverse mechanisms, including mutations affecting iron transport and cell wall biosynthesis, leading to significant phenotypic adaptations like the SCV phenotype. Continuous global surveillance is crucial to monitor the emergence of such resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1761368","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:03:29Z","timestamp":1779775409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Small colony variants and cefiderocol resistance in clinical Escherichia coli: an in vitro mechanistic study"],"prefix":"10.3389","volume":"17","author":[{"given":"Muhammad Ali","family":"Syed","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Department of Microbiology, The University of Haripur","place":["Haripur, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Pu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankang","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of Pulmonary and Critical Care Medicine, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1381511","DOI":"10.3389\/fmicb.2024.1381511","article-title":"Extensively and multidrug-resistant bacterial strains: case studies of antibiotics resistance","volume":"15","author":"Almutairy","year":"2024","journal-title":"Front. 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