Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae
Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae
复制标题
全基因组分析揭示了肺炎支原体大环内酯类耐药性的新见解
DOI：
10.3967/bes2017.045
复制
发表时间：
2017-05-01
影响因子：
3.5
通讯作者：
Zhao Han Qing
中科院分区：
文献类型：
--
作者：
Li Shao Li;Sun Hong Mei;Zhao Han Qing
目的肺炎支原体对大环内酯类抗生素耐药与23S rRNA基因突变有关。然而，仅靠这些突变并不能完全解释亚洲的高耐药率。本研究旨在探讨肺炎支原体对大环内酯类抗生素耐药的其他可能突变。方法采用Illumina HiSeq2000全基因组测序平台对10株肺炎支原体临床分离株进行全基因组测序。用利血平和间氯苯肼(CCCP)外排抑制法检测大环内酯类抗生素特异性外排转运体的作用。结果与参考菌株M129和FH相比，10株临床分离株共检测到56个单核苷酸多态(SNPs)。值得注意的是，在导致非同义突变的30个SNP中，有4个聚集在编码ATP结合盒转运体家族的大环内酯类特异性外排泵蛋白的大环内酯类排出系统基因MacB上。在大环内酯类抗生素的最小抑菌浓度(MIC)测定中，外排泵抑制剂的存在导致MIC显著降低，甚至在某些菌株的最低抑菌浓度下也是如此。结论我们的研究表明，除了23S rRNA基因的共同点突变外，大环内酯类抗生素外排泵还可能导致肺炎支原体对大环内酯类抗生素的耐药性。
Objective Mutations in 23S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae (M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae.Methods The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina HiSeq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP).Results A total of 56 single nucleotide polymorphisms (SNPs) were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene macB encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations (MIC) of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains.Conclusion Our study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23S rRNA gene.