Combination Effect of Phenylalanine-Arginine-Beta-Naphthylamide and Curcumin on the Expression of the Gene in Aminoglycoside-Resistant Clinical Isolates of

Overview

Journal Health Sci Rep

Specialty General Medicine

Date 2024 Dec 11

PMID 39659815

Authors

Parisa Charkhi

Mohammad Reza Haghshenas

Bahman Mirzaei

Younes Khalili

Hamid Reza Goli

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Overexpression of MexXY-OprM efflux pump causes resistance to aminoglycosides in . We aimed to investigate the relationship between resistance to aminoglycosides and the MexXY-OprM expression level in clinical isolates without and after treatment with curcumin and/or phenylalanine-arginine-beta-naphthylamide (PAβN) as the efflux pump inhibitors.

Methods: We collected 100 clinical isolates from hospitalized patients. The minimum inhibitory concentrations of aminoglycosides were determined by the micro-broth dilution method in the presence and absence of PAβN and/or curcumin. Then, real-time PCR was used to determine the expression level of the MexXY-OprM efflux pump.

Results: 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 gene, while 31 (68.88%) isolates exhibited a 2-3-fold overexpression, and 14 (31.11%) isolates had a more than threefold overexpression of the gene. However, 4 (8.88%) isolates showed a ≥ 10-fold overexpression of this gene. The combination of PAβN 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-, tobramycin-, kanamycin-, streptomycin-, and netilmicin-resistant isolates showed a decreased MIC range in combination with curcumin. The most synergistic effect of curcumin and PAβN was observed in combination with spectinomycin, while the least synergistic effect was detected with kanamycin.

Conclusion: Curcumin can be a significant efflux inhibitor as an adjuvant in combination with aminoglycosides for successful treatment of patients infected by overexpressing the MexXY-OprM efflux pump.

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