{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:30:23Z","timestamp":1786516223627,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      As one of the most common groups of clinical pathogens,\n                      <jats:italic>Enterobacterales<\/jats:italic>\n                      pose a serious threat to global public health due to their multidrug-resistance. Polymyxin serves as a last-line treatment for infections caused by Carbapenem-resistant\n                      <jats:italic>Enterobacterales<\/jats:italic>\n                      (CRE). The emergence and spread of the mobilized colistin resistance (\n                      <jats:italic>mcr<\/jats:italic>\n                      ) genes, particularly the globally prevalent\n                      <jats:italic>mcr-1<\/jats:italic>\n                      and\n                      <jats:italic>mcr-8<\/jats:italic>\n                      , have raised significant public health concerns. Epidemiological data reveal a striking host tropism among these genes:\n                      <jats:italic>mcr-1<\/jats:italic>\n                      is predominantly found in\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      (83.75%), while\n                      <jats:italic>mcr-8<\/jats:italic>\n                      is primarily detected in\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (92.68%). The underlying mechanisms driving this host-specific distribution and its implications for bacterial virulence remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study investigated the host-dependent fitness, transmission, and virulence effects of\n                      <jats:italic>mcr-1<\/jats:italic>\n                      and\n                      <jats:italic>mcr-8<\/jats:italic>\n                      using a combination of recombinant plasmids transformed into\n                      <jats:italic>E. coli<\/jats:italic>\n                      DH5\u03b1 and\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      ATCC 13883, alongside clinical isolates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results demonstrate that the biological cost and benefit associated with these plasmids are host-dependent. In\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      , the\n                      <jats:italic>mcr-8<\/jats:italic>\n                      plasmid exhibited enhanced stability and fitness. Conversely, the\n                      <jats:italic>mcr-1<\/jats:italic>\n                      plasmid conferred a competitive advantage in\n                      <jats:italic>E. coli<\/jats:italic>\n                      . The impact on bacterial virulence in\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      larvae infection model varied with the host strain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that the fitness, transmission potential, and virulence modulation conferred by\n                      <jats:italic>mcr-1<\/jats:italic>\n                      and\n                      <jats:italic>mcr-8<\/jats:italic>\n                      are closely associated with the bacterial host. Specifically, the\n                      <jats:italic>mcr-1<\/jats:italic>\n                      plasmid exhibits enhanced transmissibility in\n                      <jats:italic>E. coli<\/jats:italic>\n                      compared to\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      , whereas the\n                      <jats:italic>mcr-8<\/jats:italic>\n                      plasmid demonstrates a transmission advantage in\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      over\n                      <jats:italic>E. coli<\/jats:italic>\n                      . The findings of this study clarify that the preferred hosts of\n                      <jats:italic>mcr-1<\/jats:italic>\n                      and\n                      <jats:italic>mcr-8<\/jats:italic>\n                      plasmids are\n                      <jats:italic>E. coli<\/jats:italic>\n                      and\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      , respectively, and confirm that plasmid fitness, transmissibility, and virulence effects are host-dependent. These results suggest that future development of prevention and control strategies should incorporate differentiated interventions targeting distinct bacterial hosts and plasmid types, in order to more effectively curb the spread of\n                      <jats:italic>mcr<\/jats:italic>\n                      genes and extend the clinical utility of polymyxin.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1908233","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:54:40Z","timestamp":1786514080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Host-dependent effects of mcr-1 and mcr-8 on fitness, virulence, and transmission in Escherichia coli and Klebsiella pneumoniae"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengyu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"Zhejiang Provincial Engineering Research Center of Innovative Instruments for Precise Pathogen Detection","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuoyou","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangdu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]},{"name":"Zhejiang Provincial Engineering Research Center of Innovative Instruments for Precise Pathogen Detection","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Infectious 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