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While its spread is well documented, the adaptations enabling its concurrent antibiotic resistance and clinical pathogenicity remain unknown. The metabolism of bacterial pathogens has evolved to support virulence in nutrient-limiting host environments. Here, we show that sorbose metabolism promotes the fitness and virulence of\n                      <jats:italic toggle=\"yes\">mcr-1-<\/jats:italic>\n                      positive\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      (MCRPEC), but does not affect its resistance to colistin or polymyxin B. Notably, the virulence contribution is also observed in an\n                      <jats:italic toggle=\"yes\">mcr-1<\/jats:italic>\n                      -negative background. Genetic disruption of sorbose catabolism (\u0394\n                      <jats:italic toggle=\"yes\">sorD<\/jats:italic>\n                      ) attenuated MCRPEC virulence and fitness both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Integrated transcriptomic and metabolomic analyses suggest that this attenuation is associated with impaired expression of two major virulence determinants. First, defective sorbose metabolism limits the supply of monosaccharide precursors required for LPS biosynthesis, leading to reduced LPS content. Second, metabolic disruption decreases intracellular cAMP levels, which downregulates\n                      <jats:italic toggle=\"yes\">fimH<\/jats:italic>\n                      expression via a cAMP-dependent signaling pathway, thereby compromising bacterial adhesion. Notably, although\n                      <jats:italic toggle=\"yes\">sorD<\/jats:italic>\n                      deletion enhances biofilm formation, this increase is insufficient to rescue the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      virulence defect. Restoration of the sorbose metabolic pathway partially rescues MCRPEC pathogenicity. These findings suggest that sorbose metabolism contributes to MCRPEC pathogenicity by supporting LPS synthesis and regulating\n                      <jats:italic toggle=\"yes\">fimH<\/jats:italic>\n                      expression via cAMP signaling. This study indicates a metabolic link between sorbose utilization and MCRPEC pathogenicity, raising the possibility that sorbose, a common food additive, could facilitate MCRPEC pathogenicity.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The spread of colistin-resistant\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        (\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        ) limits treatment options for life-threatening infections. This study shows that sorbose metabolism, which utilizes a common dietary sugar, contributes to the fitness and virulence of such resistant bacteria without affecting their colistin resistance. Using\n                        <jats:italic toggle=\"yes\">mcr-1<\/jats:italic>\n                        -positive\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        , we find that this metabolic pathway supports lipopolysaccharide synthesis and, via a cAMP-dependent mechanism, promotes bacterial adhesion. Disabling sorbose catabolism attenuates the pathogen in animal models. These findings suggest a previously unrecognized link between a specific carbohydrate metabolism and pathogenesis in drug-resistant\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        , raising the possibility that dietary components may influence infection outcomes.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00191-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:02:01Z","timestamp":1781524921000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Sorbose metabolism promotes fitness and virulence in\n                    <i>Escherichia coli<\/i>"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7886-7017","authenticated-orcid":false,"given":"Xue","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University Shenzhen Campus","place":["Shenzhen, China"]},{"name":"Ministry of Education, Key Laboratory of Tropical Diseases Control, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0008-2647","authenticated-orcid":true,"given":"Cong","family":"Shen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qb7bg95","id-type":"ROR","asserted-by":"publisher"}],"name":"The Second Clinical Medical College, Guangzhou University of Chinese Medicine, State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/01gb3y148","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Dampness Syndrome of Chinese Medicine\/Clinical Laboratory, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University","place":["Qingyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangzhou Southern College","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Qiu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01c4jmp52","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Laboratory Medicine, Chengdu Medical College","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shenzhen People's Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University Shenzhen Campus","place":["Shenzhen, China"]},{"name":"Ministry of Education, Key Laboratory of Tropical Diseases Control, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University Shenzhen Campus","place":["Shenzhen, China"]},{"name":"Ministry of Education, Key Laboratory of Tropical 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