{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:14:26Z","timestamp":1783980866509,"version":"3.55.0"},"reference-count":72,"publisher":"Microbiology Society","issue":"6","funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"crossref","award":["17\/372"],"award-info":[{"award-number":["17\/372"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,16]]},"abstract":"\n Introduction.<\/jats:bold> Aminoglycoside antibiotics are widely used to treat infections of \n \n Pseudomonas aeruginosa<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>. The MexXY-OprM efflux pump is an important contributor to aminoglycoside tolerance in \n \n P. aeruginosa<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> reference strains and expression of the mexXY<\/jats:italic> genes is repressed by the MexZ repressor protein. Direct investigation of the role of this efflux pump in clinical isolates is relatively limited.<\/jats:p>\n \n Hypothesis.<\/jats:bold> The contribution of MexXY-OprM to \n \n P. aeruginosa<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> aminoglycoside resistance is isolate-specific.<\/jats:p>\n \n Aim.<\/jats:bold> To quantify the role of MexXY-OprM and its repressor, MexZ, in clinical isolates of P. aeruginosa.<\/jats:italic>\n <\/jats:p>\n \n Methodology.<\/jats:bold> The mexXY<\/jats:italic> genes were deleted from ten clinical isolates of \n \n P. aeruginosa<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>, and the mexZ<\/jats:italic> gene from nine isolates. Antimicrobial susceptibility testing was carried out for commonly used antipseudomonal drugs on the engineered mutants and the isogenic wild-type isolates. RT-qPCR was used to measure expression of the mexX<\/jats:italic> gene.<\/jats:p>\n \n Results.<\/jats:bold> All but one of the mexXY<\/jats:italic> mutants were more susceptible to the clinically used aminoglycosides tobramycin, gentamicin and amikacin but the degree to which susceptibility increased varied greatly between isolates. The mexXY<\/jats:italic> mutants were also more susceptible to a fluoroquinolone, ciprofloxacin. In three isolates with functional MexZ, deletion of mexZ<\/jats:italic> increased expression of mexXY<\/jats:italic> and aminoglycoside tolerance. Conversely, deleting mexZ<\/jats:italic> from six clinical isolates with mexZ<\/jats:italic> sequence variants had little or no effect on expression of mexXY<\/jats:italic> or on aminoglycoside susceptibility, consistent with the variants abolishing MexZ function. Genome analysis showed that over 50\u200a% of 619 clinical isolates had sequence variants predicted to reduce the affinity of MexZ for DNA, likely increasing mexXY<\/jats:italic> expression and hence efflux of aminoglycosides.<\/jats:p>\n \n Conclusion.<\/jats:bold> Our findings show that the interplay between MexXY, MexZ and the level of mexXY<\/jats:italic> expression plays an important role in aminoglycoside resistance in clinical isolates of \n \n P. aeruginosa<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> but the magnitude of the contribution of this efflux pump to resistance is isolate-specific.<\/jats:p>","DOI":"10.1099\/jmm.0.001551","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T17:17:51Z","timestamp":1655399871000},"source":"Crossref","is-referenced-by-count":22,"title":["Aminoglycoside resistance in Pseudomonas aeruginosa: the contribution of the MexXY-OprM efflux pump varies between 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