National Center of Hematology and Transfusion, Central Blood Bank of Azerbaijan, Baku, Azerbaijan.
Department of Medical Microbiology, Ondokuz Mayis University Medical School, Samsun, Turkey.
J Chemother. 2023 Nov;35(7):601-609. doi: 10.1080/1120009X.2023.2173857. Epub 2023 Jan 30.
Resistance and tolerance to antituberculosis drugs have become serious problems in disease treatment. This multi-phase study investigated the contributions of efflux pumps to drug resistance. In the first phase, the minimum inhibitory concentration (MIC) levels of antibiotics were determined. In the second phase, MIC levels were determined in the presence of the efflux pump inhibitors carbonyl cyanide m-chlorophenyl hydrazone (CCCP), verapamil, reserpine and thioridazine. In the third phase, MIC levels were reduced in 6 isolates in the presence of efflux pump inhibitors to determine the expression of putative efflux pump genes by reverse transcriptase-polymerase chain reaction (RT-PCR). MIC levels of fluoroquinolones decreased in 6 (6.52%) isolates, MIC of rifampicin in 4 (4.34%), and MIC of streptomycin in 3 (3.26%) in the presence of efflux pump inhibitors reserpine, CCCP and verapamil. The efflux pump inhibitors CCCP, verapamil, and reserpine changed MICs 2- to 16-fold. Overexpression of all 15 efflux pump genes was observed in 6 isolates with a reduction in MIC values in the presence of efflux pump inhibitors. The overexpression of efflux-related genes in resistant isolates suggests that efflux pumps are associated with resistance development.
抗结核药物的耐药性和耐受性已成为疾病治疗中的严重问题。这项多阶段研究调查了外排泵对药物耐药性的贡献。在第一阶段，确定抗生素的最小抑菌浓度（MIC）水平。在第二阶段，在存在外排泵抑制剂羰基氰化物 m-氯苯腙（CCCP）、维拉帕米、利血平和噻氯匹定的情况下确定 MIC 水平。在第三阶段，在存在外排泵抑制剂的情况下，6 个分离株的 MIC 水平降低，以通过逆转录-聚合酶链反应（RT-PCR）确定推定外排泵基因的表达。在存在外排泵抑制剂利血平、CCCP 和维拉帕米的情况下，氟喹诺酮类药物的 MIC 水平在 6 个（6.52%）分离株中降低，利福平的 MIC 在 4 个（4.34%）中降低，链霉素的 MIC 在 3 个（3.26%）中降低。外排泵抑制剂 CCCP、维拉帕米和利血平将 MIC 改变了 2 至 16 倍。在存在外排泵抑制剂的情况下，MIC 值降低，在 6 个分离株中观察到所有 15 个外排泵基因的过度表达。耐药分离株中外排相关基因的过度表达表明外排泵与耐药性的发展有关。
