基于全基因组重测序技术的浙江近岸海域耐盐金黄色葡萄球菌(Staphylococcus aureus)耐药机制解析

ANALYSIS OF THE DRUG RESISTANCE MECHANISM OF STAPHYLOCOCCUS AUREUS BASED ON WHOLE-GENOME RESEQUENCING TECHNOLOGY

金黄色葡萄球菌(Staphylococcus aureus)是近岸海域海水中的主要病原菌,严重威胁接触者的安全。抗生素处理是治疗金黄色葡萄球菌感染的重要手段,其耐药性的发生受到了高度重视。采用全基因组重测序与KEGG富集分析结合的方法,对红霉素(erythromycin)、氯霉素(chloramphenicol)和万古霉素(vancomycin)处理后的耐盐金黄色葡萄球菌(S.aureus ZS01)和不耐盐金黄色葡萄球菌(S.aureus 502A)进行耐药机制研究。结果表明,S.aureus 502A经抗生素处理后发生突变的程度大于S.aureus ZS01,二者在经过氯霉素处理发生了更大程度的突变。红霉素、氯霉素和万古霉素处理主要影响了金黄色葡萄球菌的致病能力;红霉素和氯霉素可能通过影响金黄色葡萄球菌脂类的代谢引起其耐药性的变化。除此之外,三种抗生素处理均出现了较多TIGR01741家族蛋白和假设蛋白基因的突变,推测与菌株的耐药性和致病性相关。耐盐金黄色葡萄球菌可通过外排系统作用产生红霉素耐药性,不耐盐菌株因细胞壁成分相关基因的突变提高了对万古霉素的耐受性。研究结果可为耐盐和不耐盐金黄色葡萄球菌的耐药机制及抗生素对金黄色葡萄球菌致病性影响的研究提供基础数据。

Staphylococcus aureus is the main common pathogen in coastal waters,and could seriously threatens the safety of the contactees.Antibiotic treatment is an important method for the treatment of S.aureus infection;and however,the occurrence of its drug resistance has been highly concerned.In this paper,a combination of whole-genome resequencing and KEGG enrichment analysis was combined used to analyze the resistance mechanism of salt-tolerant S.aureus ZS01 and salt-intolerant S.aureus 502A treated with erythromycin,chloramphenicol,and vancomycin.Results showed that compared with S.aureus ZS01,S.aureus 502A had showed more mutations after antibiotic treatment,and both of them had more variation after treated with chloramphenicol.Erythromycin,chloramphenicol and vancomycin treatments affected mainly the pathogenicity of S.aureus.Erythromycin and chloramphenicol may affect the lipid metabolism of S.aureus and make caused changes in drug resistance.In addition,there were many mutations of TIGR01741 family proteins and hypothetical protein genes in the three antibiotic treatments,which are speculated to be related to the drug resistance and pathogenicity of the strains.Salt-tolerant S.aureus could develop erythromycin resistance through efflux system,and salt-intolerant strain also could increase their tolerance to vancomycin due to mutations in genes related to cell wall components.The results of this study can provide basic data for understanding the study of the resistance mechanism of salt-tolerant and salt-intolerant S.aureus and the effect of antibiotics on the pathogenicity of S.aureus.