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Comparative genomic analysis of multidrug-resistant Streptococcus pneumoniae isolates

机译：耐多药肺炎链球菌分离株的基因组比较分析

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Introduction: Multidrug resistance in Streptococcus pneumoniae has emerged as a serious problem to public health. A further understanding of the genetic diversity in antibiotic-resistant S. pneumoniae isolates is needed. Methods: We conducted whole-genome resequencing for 25 pneumococcal strains isolated from children with different antimicrobial resistance profiles. Comparative analysis focus on detection of single-nucleotide polymorphisms (SNPs) and insertions and deletions (indels) was conducted. Moreover, phylogenetic analysis was applied to investigate the genetic relationship among these strains. Results: The genome size of the isolates was ~2.1 Mbp, covering >90% of the total estimated size of the reference genome. The overall G+C% content was ~39.5%, and there were 2,200–2,400 open reading frames. All isolates with different drug resistance profiles harbored many indels (range 131–171) and SNPs (range 16,103–28,128). Genetic diversity analysis showed that the variation of different genes were associated with specific antibiotic resistance. Known antibiotic resistance genes ( pbps , murMN , ciaH , rplD , sulA , and dpr ) were identified, and new genes ( regR , argH , trkH , and PTS-EII ) closely related with antibiotic resistance were found, although these genes were primarily annotated with functions in virulence as well as carbohydrate and amino acid transport and metabolism. Phylogenetic analysis unambiguously indicated that isolates with different antibiotic resistance profiles harbored similar genetic backgrounds. One isolate, 14-LC.ER1025, showed a much weaker phylogenetic relationship with the other isolates, possibly caused by genomic variation. Conclusion: In this study, although pneumococcal isolates had similar genetic backgrounds, strains were diverse at the genomic level. These strains exhibited distinct variations in their indel and SNP compositions associated with drug resistance.
机译：简介：肺炎链球菌的多药耐药性已成为公共卫生的严重问题。需要对耐药性肺炎链球菌分离株的遗传多样性有进一步的了解。方法：我们对25株肺炎球菌菌株进行了全基因组重测序，这些菌株是从具有不同抗药性的儿童中分离出来的。比较分析的重点是检测单核苷酸多态性（SNP）和插入和缺失（indels）。此外，系统发育分析用于调查这些菌株之间的遗传关系。结果：分离株的基因组大小约为2.1 Mbp，占参考基因组总估计大小的90％以上。总体G + C％含量约为39.5％，并且有2,200–2,400个开放阅读框。具有不同耐药性的所有分离株均具有许多插入缺失（范围131–171）和SNP（范围16,103–28,128）。遗传多样性分析表明，不同基因的变异与特定的抗生素抗性有关。鉴定了已知的抗生素抗性基因（pbps，murMN，ciaH，rplD，sulA和dpr），并发现了与抗生素抗性密切相关的新基因（regR，argH，trkH和PTS-EII），尽管这些基因主要被注释具有毒力以及碳水化合物和氨基酸的运输和代谢功能。系统发育分析明确表明，具有不同抗生素抗性谱的分离株具有相似的遗传背景。一种分离株14-LC.ER1025与其他分离株的系统发生关系较弱，可能是由于基因组变异所致。结论：在这项研究中，尽管肺炎球菌分离株具有相似的遗传背景，但菌株在基因组水平上是不同的。这些菌株在其indel和SNP组成上显示出与耐药性有关的明显变化。

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