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MexXY efflux pump plays an important role in bacterial resistance and tolerance to aminoglycoside antibiotics. tRNA nucleotidyltransferase (Cca, CCA-adding enzyme) is a universal polymerase responsible for the synthesis and repair of the 3\u2032-terminal CCA sequence of tRNA. In this study, we found that mutation of the\n                      <jats:italic toggle=\"yes\">cca<\/jats:italic>\n                      gene increases resistance and tolerance to aminoglycosides in\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . We demonstrate that the upregulation of\n                      <jats:italic toggle=\"yes\">mexXY<\/jats:italic>\n                      genes contributes to the increased resistance and tolerance of the \u0394\n                      <jats:italic toggle=\"yes\">cca<\/jats:italic>\n                      mutant. Furthermore, our experimental results revealed that Cca controls the transcription of\n                      <jats:italic toggle=\"yes\">armZ<\/jats:italic>\n                      , which encodes a positive regulator of\n                      <jats:italic toggle=\"yes\">mexXY<\/jats:italic>\n                      , through its leader peptide PA5471.1. An increased amount of\n                      <jats:italic toggle=\"yes\">PA5471.1<\/jats:italic>\n                      mRNA was found to be associated with ribosomes in the \u0394\n                      <jats:italic toggle=\"yes\">cca<\/jats:italic>\n                      mutant, indicating enhanced ribosome stalling. In addition, we found that the glutamine and phenylalanine at the third and fourth codons of PA5471.1, respectively, are involved in the Cca-mediated transcriptional upregulation of\n                      <jats:italic toggle=\"yes\">armZ<\/jats:italic>\n                      . Therefore, our data reveal the molecular mechanism of Cca-mediated regulation of aminoglycoside susceptibility in\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01653-25","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T14:54:37Z","timestamp":1772549677000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Pseudomonas aeruginosa<\/i>\n                    tRNA nucleotidyltransferase Cca controls resistance and tolerance to aminoglycoside antibiotics by regulating the MexXY multidrug efflux pump"],"prefix":"10.1128","volume":"70","author":[{"given":"Chenyu","family":"Shen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of 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