西藏牦牛源牛支原体对大环内酯类抗生素的耐药机制  

Resistance mechanism of Mycoplasma Bovis from Xizang yak to macrolide antibiotics

作　　者：罗婷 韩著 徐业芬 徐晋花 任才 索朗斯珠 牛家强 LUO Ting;HAN Zhu;XU Yefen;XU Jinhua;REN Cai;SUOLANG Sizhu;NIU Jiaqiang(Xizang Key Laboratory of Hydatidosis Control,Ministry of Agriculture and Rural Areas/Provincial Key Laboratory of Xizang Plateau Animal Epidemic Disease Research,College of Animal Sciences,Xizang Agriculture and Animal Husbandry College,Linzhi,Xizang 860000,China)

机构地区：[1]西藏农牧学院动物科学学院农业农村部西藏包虫病防治重点实验室/西藏高原动物疫病研究自治区高校重点实验室,西藏林芝860000

出　　处：《中国兽医学报》2024年第11期2371-2378,共8页Chinese Journal of Veterinary Science

基　　金：西藏农牧学院研究生教育创新计划资助项目(YJS2023-20);西藏自治区重点研发计划资助项目(XZ202001ZY0046N);财政部和农业农村部“国家现代农业产业技术体系”资助项目(CARS-37)

摘　　要：采用微量法对10株西藏牦牛源牛支原体进行了大环内酯类抗生素的药物敏感性试验,并对敏感株进行了体外高度耐药株的诱导,对敏感株、耐药株和体外高度耐药株进行了靶位基因突变分析,甲基化酶基因、钝化酶基因以及药物主动外排系统的检测,以揭示大环内酯类药物耐药机制。结果显示:10株牛支原体对大环内酯类抗生素均存在不同程度的耐药性,但经过甲基化酶和钝化酶基因检测分析,发现均不存在甲基化酶基因编码的甲基化酶和大环内酯类钝化酶介导的耐药机制,说明敏感株和耐药株的靶位基因位点均未发生突变;而体外高度耐药株在Domain-Ⅱ、L22和L4靶位基因位点发生了突变,从而说明若存在2个及2个以上靶位基因氨基酸位点发生突变,则可产生高度耐药株;经过主动外排系统检测,发现均不存在以大环内酯类抗生素为底物的主动外排系统。由此可见,西藏牦牛源牛支原体在大环内酯类药物高浓度的压力下,菌株容易发生突变,且存在2个及2个以上靶位基因氨基酸位点发生突变,则容易产生高度耐药株。The purpose of this study was to reveal the resistance mechanism of Mycoplasma bovis from Xizang yaks to macrolide antibiotics and provide theoretical basis for clinical medication.In this study,10 strains of Mycoplasma bovis from Xizang yaks were tested for drug sensitivity to macrolide antibiotics using the micromethod,and sensitive strains were induced to be highly resistant in vitro.The results showed that all 10 strains of Mycoplasma bovis exhibited varying degrees of resistance to macrolide antibiotics.However,through methylation enzyme and inactivation enzyme gene detection and analysis,it was found that there was no methylation enzyme encoded by the methylation enzyme gene and no resistance mechanism mediated by macrolide inactivation enzymes,indicating that there were no mutations in the target gene loci of the sensitive and resistant strains.However,highly resistant strains in vitro have mutations at the domainⅡ,L22,and even L4 target gene loci,indicating that if two or more target gene amino acid loci undergo mutations,highly resistant strains can be produced.After testing with active efflux systems,it was found that there were no active efflux systems using macrolide antibiotics as substrates.It can be seen that the strain of Mycoplasma bovis from Xizang yaks is prone to mutation under the pressure of high concentrations of macrolides,and there are mutations in two or more target gene amino acid sites,which is prone to produce highly resistant strains.

关 键 词：牦牛源 牛支原体 大环内酯类抗生素 基因位点突变 耐药机制 

分 类 号：S852.62[农业科学—基础兽医学]