次抑菌浓度大环内酯类药物诱导肺炎支原体耐药机制研究

发布时间：2018-03-28 13:39

本文选题：肺炎支原体　切入点：大环内酯类药物　出处：《中国病原生物学杂志》2016年01期

【摘要】：目的研究次抑菌浓度的大环内酯类抗生素对肺炎支原体(Mycoplasma pneumoniae,Mp)敏感株耐药的诱导作用,并探讨Mp的耐药机制。方法对104株Mp临床株进行药物敏感试验,检测5种常见大环内酯类抗生素对Mp临床分离株的最小抑菌浓度(Minimum inhibitory concentration,MIC),筛选Mp敏感株;分别用次抑菌浓度的红霉素、阿奇霉素和吉他霉素对Mp敏感株诱导10代后,比较诱导前后Mp株的MIC值,分析耐药诱导情况;PCR扩增诱导前后Mp株耐药决定区基因并进行序列测定,通过BLAST软件对编码序列进行比对,分析诱导前后耐药决定区基因23SrRNA,核糖体蛋白L4和L22的突变情况。结果 104株Mp临床株中共分离出11株大环内酯类抗生素敏感株,经诱导耐药后有2株存在核糖体蛋白L22T279C突变;3株存在核糖体蛋白L4突变,其中两株存在C162A、A430G突变,1株存在A209T突变。未检出23SrRNA基因突变。结论次抑菌浓度的大环内酯类药物可诱导Mp耐药,其诱导耐药机制可能与核糖体L4及L22基因突变有关。
[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.
【作者单位】：邵阳医学高等专科学校;南华大学病原生物学研究所;
【基金】：湖南省科技计划项目(No.2013FJ3067) 湖南省邵阳市科技局基金项目(No.Z1203)
【分类号】：R446.5

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