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Here, we investigated the transcriptomic and phenotypic responses of\n                      <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                      ATCC19606 mutants lacking the efflux pumps AdeAB, AdeIJ, or CraA under chloramphenicol stress. The deletion of\n                      <jats:italic toggle=\"yes\">craA<\/jats:italic>\n                      resulted in a 32-fold reduction in chloramphenicol MIC, while \u0394\n                      <jats:italic toggle=\"yes\">adeIJ<\/jats:italic>\n                      showed a modest 4-fold decrease, and \u0394\n                      <jats:italic toggle=\"yes\">adeAB<\/jats:italic>\n                      had no effect on chloramphenicol susceptibility. Transcriptomic profiling revealed minimal alterations in \u0394\n                      <jats:italic toggle=\"yes\">craA<\/jats:italic>\n                      , but notable transcriptional reprogramming in \u0394\n                      <jats:italic toggle=\"yes\">adeAB<\/jats:italic>\n                      and \u0394\n                      <jats:italic toggle=\"yes\">adeIJ<\/jats:italic>\n                      , including upregulation of ribosomal genes, iron-sulfur cluster biogenesis, aromatic compound catabolism, and amino acid transport systems. Under chloramphenicol stress, \u0394\n                      <jats:italic toggle=\"yes\">adeAB<\/jats:italic>\n                      exhibited metabolic remodeling, activating oxidative stress defenses and protein quality control pathways while repressing type VI secretion. Both \u0394\n                      <jats:italic toggle=\"yes\">adeIJ<\/jats:italic>\n                      and wild-type strains upregulated arginine and glutamate metabolism, likely contributing to redox balance. Phenotypically, the \u0394\n                      <jats:italic toggle=\"yes\">adeIJ<\/jats:italic>\n                      strain showed elevated basal and H\u2082O\u2082-induced ROS levels, as well as heightened sensitivity to nitrosative stress and Cu\n                      <jats:sup>2+<\/jats:sup>\n                      , which may suggest a role for AdeIJ in oxidative and metal stress responses. Despite increased\n                      <jats:italic toggle=\"yes\">adeAB<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">craA<\/jats:italic>\n                      expression under chloramphenicol stress, only\n                      <jats:italic toggle=\"yes\">craA<\/jats:italic>\n                      deletion significantly impaired resistance, highlighting its dominant role in chloramphenicol efflux. Collectively, our findings reveal efflux pump-specific and strain-specific adaptations to antibiotic stress, positioning CraA as a major determinant of chloramphenicol resistance, while RND transporters such as AdeABC and AdeIJK may also be associated with broader stress adaptation processes, including redox and metal homeostasis, in\n                      <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Efflux pumps are key drivers of multidrug resistance in\n                        <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                        , yet their broader roles in stress adaptation remain insufficiently understood. Here, we show that the loss of major efflux systems reshapes the transcriptomic and metabolic landscape under chloramphenicol stress, a condition that also imposes oxidative stress. In particular, the RND efflux pump AdeIJK may be linked to alterations in cellular responses to oxidative, nitrosative, and metal stress, although the mechanistic basis of this interplay remains to be further investigated. Overall, these findings suggest that efflux pumps may contribute to bacterial resilience beyond drug resistance, providing additional insight into efflux system hierarchy and functional redundancy in\n                        <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                        , and may inform future studies aimed at understanding persistence and efflux-mediated multidrug resistance mechanisms.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00009-26","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:00:52Z","timestamp":1788440452000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Chloramphenicol stress triggers oxidative adaptation in\n                    <i>Acinetobacter baumannii<\/i>\n                    ATCC19606 devoid of RND efflux pumps AdeAB or 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