{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:29:19Z","timestamp":1791811759618,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004160","name":"Mazandaran University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Overexpression of MexXY\u2010OprM efflux pump causes resistance to aminoglycosides in <jats:italic>Pseudomonas aeruginosa<\/jats:italic>. We aimed to investigate the relationship between resistance to aminoglycosides and the MexXY\u2010OprM expression level in <jats:italic>P. aeruginosa<\/jats:italic> clinical isolates without and after treatment with curcumin and\/or phenylalanine\u2010arginine\u2010beta\u2010naphthylamide (PA\u03b2N) as the efflux pump inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected 100 clinical isolates from hospitalized patients. The minimum inhibitory concentrations of aminoglycosides were determined by the micro\u2010broth dilution method in the presence and absence of PA\u03b2N and\/or curcumin. Then, real\u2010time PCR was used to determine the expression level of the MexXY\u2010OprM efflux pump.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, 34%, 35%, 10%, 38%, 43%, 42%, and 39% of the clinical isolates were resistant to gentamicin, tobramycin, amikacin, netilmicin, spectinomycin, kanamycin, and streptomycin, respectively. Also, 45% of the isolates showed an overexpression of the <jats:italic>mexY<\/jats:italic> gene, while 31 (68.88%) isolates exhibited a 2\u20133\u2010fold overexpression, and 14 (31.11%) isolates had a more than threefold overexpression of the <jats:italic>mexY<\/jats:italic> gene. However, 4 (8.88%) isolates showed a \u2265\u200910\u2010fold overexpression of this gene. The combination of PA\u03b2N with spectinomycin, netilmicin, streptomycin, and kanamycin exhibited a reduced MIC range of these aminoglycosides in 93.02%, 86.8%, 76.9%, and 71.4% of resistant isolates, respectively. Additionally, all gentamicin\u2010, tobramycin\u2010, kanamycin\u2010, streptomycin\u2010, and netilmicin\u2010resistant isolates showed a decreased MIC range in combination with curcumin. The most synergistic effect of curcumin and PA\u03b2N was observed in combination with spectinomycin, while the least synergistic effect was detected with kanamycin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Curcumin can be a significant efflux inhibitor as an adjuvant in combination with aminoglycosides for successful treatment of patients infected by <jats:italic>P. aeruginosa<\/jats:italic> overexpressing the MexXY\u2010OprM efflux pump.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.70255","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T09:46:01Z","timestamp":1733823961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combination Effect of Phenylalanine\u2010Arginine\u2010Beta\u2010Naphthylamide and Curcumin on the Expression of the <i>mexY<\/i> Gene in Aminoglycoside\u2010Resistant Clinical Isolates of <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1002","volume":"7","author":[{"given":"Parisa","family":"Charkhi","sequence":"first","affiliation":[{"name":"Molecular and Cell Biology Research Centre, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"},{"name":"Department of Medical Microbiology and Virology, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Haghshenas","sequence":"additional","affiliation":[{"name":"Molecular and Cell Biology Research Centre, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"},{"name":"Department of Medical Microbiology and Virology, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahman","family":"Mirzaei","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Virology, School of Medicine Zanjan University of Medical Sciences Zanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younes","family":"Khalili","sequence":"additional","affiliation":[{"name":"Immunology Research Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-1911","authenticated-orcid":false,"given":"Hamid Reza","family":"Goli","sequence":"additional","affiliation":[{"name":"Molecular and Cell Biology Research Centre, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"},{"name":"Department of Medical Microbiology and Virology, Faculty of Medicine Mazandaran University of Medical Sciences Sari 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