{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:10:14Z","timestamp":1785431414607,"version":"3.56.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The past decade has witnessed the emergence and spread of carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                      complex (CRECC), presenting a significant clinical challenge and urgently demanding new treatment strategies against antimicrobial resistance (AMR). This study focused on the impact of tigecycline on the susceptibility of CRECC isolates to colistin and the collateral sensitivity in CRECC. Under tigecycline pressure, the resistance of five clinically isolated CRECC strains to colistin was converted from resistance to sensitivity. These mutants exhibited significantly higher expression of\n                      <jats:italic toggle=\"yes\">acrA, acrB<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">ramA<\/jats:italic>\n                      genes, with mutations in the\n                      <jats:italic toggle=\"yes\">ramR<\/jats:italic>\n                      gene. Overexpression of\n                      <jats:italic toggle=\"yes\">ramA<\/jats:italic>\n                      in certain mutants did not alter\n                      <jats:italic toggle=\"yes\">ramR<\/jats:italic>\n                      expression. No mutations were identified in lipid A synthesis genes; however,\n                      <jats:italic toggle=\"yes\">phoQ<\/jats:italic>\n                      was consistently downregulated, and\n                      <jats:italic toggle=\"yes\">arnA<\/jats:italic>\n                      expression varied among CRECC405-resistant mutants. Low-dose colistin and tigecycline combination therapy outperformed monotherapy in antimicrobial efficacy. Overall, collateral susceptibility to tigecycline was observed in CRECC isolates with colistin resistance. The overexpression of\n                      <jats:italic toggle=\"yes\">acrA, acrB,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">ramA<\/jats:italic>\n                      , due to\n                      <jats:italic toggle=\"yes\">ramR<\/jats:italic>\n                      mutations, led to tigecycline resistance. Inconsistent expression levels of lipid A synthesis genes affected lipid A modification, which in turn upregulated\n                      <jats:italic toggle=\"yes\">arnA<\/jats:italic>\n                      expression in CRECC405-resistant mutants. Increased sensitivity to colistin was associated with the downregulation of\n                      <jats:italic toggle=\"yes\">phoQ<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">arnA<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Antimicrobial resistance (AMR) is escalating faster than our ability to manage bacterial infections, with antibiotic-resistant bacteria emerging as a significant public health risk. Innovative strategies are urgently needed to curb AMR dissemination. Our research identified collateral sensitivity in\n                      <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                      complex following tigecycline (TGC) resistance, resulting in newfound sensitivity to colistin (COL), a drug to which it was once resistant. Synergistic tigecycline and colistin therapy significantly suppress bacterial growth, offering a promising approach to combat infections and curb AMR progression through the strategic pairing of antibiotics with complementary sensitivities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03310-24","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:00:37Z","timestamp":1747990837000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Study on collateral sensitivity of tigecycline to colistin-resistant\n                    <i>Enterobacter cloacae<\/i>\n                    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