Charkhi Parisa, Haghshenas Mohammad Reza, Mirzaei Bahman, Khalili Younes, Goli Hamid Reza
Molecular and Cell Biology Research Centre, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran.
Department of Medical Microbiology and Virology, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran.
Health Sci Rep. 2024 Dec 10;7(12):e70255. doi: 10.1002/hsr2.70255. eCollection 2024 Dec.
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.
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.
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.
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.
MexXY-OprM外排泵的过表达导致对氨基糖苷类药物产生耐药性。我们旨在研究在未用姜黄素和/或苯丙氨酸-精氨酸-β-萘酰胺（PAβN）作为外排泵抑制剂治疗以及治疗后的临床分离株中，对氨基糖苷类药物的耐药性与MexXY-OprM表达水平之间的关系。
我们从住院患者中收集了100株临床分离株。通过微量肉汤稀释法在有和无PAβN和/或姜黄素的情况下测定氨基糖苷类药物的最低抑菌浓度。然后，使用实时PCR来测定MexXY-OprM外排泵的表达水平。
在本研究中，临床分离株中分别有34%、35%、10%、38%、43%、42%和39%对庆大霉素、妥布霉素、阿米卡星、奈替米星、壮观霉素、卡那霉素和链霉素耐药。此外，45%的分离株显示该基因过表达，而31株（68.88%）分离株呈现2至3倍的过表达，14株（31.11%）分离株该基因有超过三倍的过表达。然而，4株（8.88%）分离株该基因显示≥10倍的过表达。PAβN与壮观霉素、奈替米星、链霉素和卡那霉素联合使用时，分别在93.02%、86.8%、76.9%和71.4%的耐药分离株中使这些氨基糖苷类药物的最低抑菌浓度范围降低。此外，所有对庆大霉素、妥布霉素、卡那霉素、链霉素和奈替米星耐药的分离株与姜黄素联合使用时最低抑菌浓度范围均降低。姜黄素和PAβN与壮观霉素联合使用时观察到的协同作用最强，而与卡那霉素联合使用时检测到的协同作用最弱。
姜黄素作为一种外排抑制剂，与氨基糖苷类药物联合使用时可作为辅助药物，用于成功治疗因MexXY-OprM外排泵过表达而感染的患者。
