次抑菌濃度大環(huán)內(nèi)酯類藥物誘導(dǎo)肺炎支原體耐藥機制研究
發(fā)布時間:2018-03-28 13:39
本文選題:肺炎支原體 切入點:大環(huán)內(nèi)酯類藥物 出處:《中國病原生物學(xué)雜志》2016年01期
【摘要】:目的研究次抑菌濃度的大環(huán)內(nèi)酯類抗生素對肺炎支原體(Mycoplasma pneumoniae,Mp)敏感株耐藥的誘導(dǎo)作用,并探討Mp的耐藥機制。方法對104株Mp臨床株進行藥物敏感試驗,檢測5種常見大環(huán)內(nèi)酯類抗生素對Mp臨床分離株的最小抑菌濃度(Minimum inhibitory concentration,MIC),篩選Mp敏感株;分別用次抑菌濃度的紅霉素、阿奇霉素和吉他霉素對Mp敏感株誘導(dǎo)10代后,比較誘導(dǎo)前后Mp株的MIC值,分析耐藥誘導(dǎo)情況;PCR擴增誘導(dǎo)前后Mp株耐藥決定區(qū)基因并進行序列測定,通過BLAST軟件對編碼序列進行比對,分析誘導(dǎo)前后耐藥決定區(qū)基因23SrRNA,核糖體蛋白L4和L22的突變情況。結(jié)果 104株Mp臨床株中共分離出11株大環(huán)內(nèi)酯類抗生素敏感株,經(jīng)誘導(dǎo)耐藥后有2株存在核糖體蛋白L22T279C突變;3株存在核糖體蛋白L4突變,其中兩株存在C162A、A430G突變,1株存在A209T突變。未檢出23SrRNA基因突變。結(jié)論次抑菌濃度的大環(huán)內(nèi)酯類藥物可誘導(dǎo)Mp耐藥,其誘導(dǎo)耐藥機制可能與核糖體L4及L22基因突變有關(guān)。
[Abstract]:Objective to study the induction of mycoplasma pneumoniae mycoplasma mycoplasma pneumoniae MP resistance by macrolide antibiotics with secondary inhibitory concentration, and to explore the mechanism of resistance to mycoplasma pneumoniae MP. Methods 104 clinical strains of mycoplasma pneumoniae MP were tested for drug sensitivity. The minimal inhibitory concentration of five common macrolides against MP clinical isolates was determined to screen the strains sensitive to MP, after 10 generations were induced by erythromycin, azithromycin and guitar mycin, respectively. The MIC value of MP strain before and after induction was compared, and the drug resistance induction was analyzed. The gene of drug resistance determinant region was amplified and sequenced before and after induction. The coding sequence was compared by BLAST software. The mutations of 23s rRNA, ribosomal protein L4 and L22 were analyzed before and after induction. Results A total of 11 macrolide antibiotic sensitive strains were isolated from 104 clinical strains of MP. After induction of drug resistance, two strains of ribosomal protein L22T279C mutation and three strains of ribosomal protein L4 mutation were found. Two of them had a mutation of A209T and one of them had a mutation of A209T. No mutation of 23SrRNA gene was detected. Conclusion the secondary inhibitory concentration of macrolides can induce Mp-resistance, and the mechanism of inducing resistance may be related to the mutation of ribosomal L4 and L22 genes.
【作者單位】: 邵陽醫(yī)學(xué)高等專科學(xué)校;南華大學(xué)病原生物學(xué)研究所;
【基金】:湖南省科技計劃項目(No.2013FJ3067) 湖南省邵陽市科技局基金項目(No.Z1203)
【分類號】:R446.5
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