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对从马来西亚一家医院收集的十株临床肺炎链球菌进行比较基因组分析,通过全基因组测序发现了 31 个新的独特的耐药性 SNP。

Comparative genomic analysis of ten clinical Streptococcus pneumoniae collected from a Malaysian hospital reveal 31 new unique drug-resistant SNPs using whole genome sequencing.

机构信息

Department of Medical Microbiology, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Department of Biological Sciences, School of Science and Technology, Sunway University, 47500, Kuala Lumpur, Malaysia.

出版信息

J Biomed Sci. 2018 Feb 15;25(1):15. doi: 10.1186/s12929-018-0414-8.

Abstract

BACKGROUND

Streptococcus pneumoniae or pneumococcus is a leading cause of morbidity and mortality worldwide, specifically in relation to community-acquired pneumonia. Due to the overuse of antibiotics, S. pneumoniae has developed a high degree of resistance to a wide range of antibacterial drugs.

METHODS

In this study, whole genome sequencing (WGS) was performed for 10 clinical strains of S. pneumoniae with different levels of sensitivity to standard antibiotics. The main objective was to investigate genetic changes associated with antibiotic resistance in S. pneumoniae.

RESULTS

Our results showed that resistant isolates contain a higher number of non-synonymous single nucleotide polymorphisms (SNPs) as compared to susceptible isolates. We were able to identify SNPs that alter a single amino acid in many genes involved in virulence and capsular polysaccharide synthesis. In addition, 90 SNPs were only presented in the resistant isolates, and 31 SNPs were unique and had not been previously reported, suggesting that these unique SNPs could play a key role in altering the level of resistance to different antibiotics.

CONCLUSION

Whole genome sequencing is a powerful tool for comparing the full genome of multiple isolates, especially those closely related, and for analysing the variations found within antibiotic resistance genes that lead to differences in antibiotic sensitivity. We were able to identify specific mutations within virulence genes related to resistant isolates. These findings could provide insights into understanding the role of single nucleotide mutants in conferring drug resistance.

摘要

背景

肺炎链球菌(Streptococcus pneumoniae)或肺炎球菌是全球发病率和死亡率的主要原因,特别是与社区获得性肺炎有关。由于抗生素的过度使用,肺炎链球菌对广泛的抗菌药物产生了高度耐药性。

方法

本研究对 10 株对标准抗生素敏感性不同的临床肺炎链球菌株进行了全基因组测序(WGS)。主要目的是研究肺炎链球菌中与抗生素耐药性相关的遗传变化。

结果

我们的结果表明,耐药分离株比敏感分离株含有更多的非同义单核苷酸多态性(SNPs)。我们能够鉴定出许多与毒力和荚膜多糖合成相关的基因中单个氨基酸发生改变的 SNPs。此外,90 个 SNPs 仅存在于耐药分离株中,31 个 SNPs 是独特的,以前没有报道过,这表明这些独特的 SNPs 可能在改变对不同抗生素的耐药水平方面发挥关键作用。

结论

全基因组测序是比较多个分离株,特别是密切相关的分离株的全基因组,以及分析导致抗生素敏感性差异的抗生素耐药基因内发现的变异的强大工具。我们能够鉴定出与耐药分离株相关的毒力基因内的特定突变。这些发现可以帮助我们理解单核苷酸突变体在赋予药物耐药性方面的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c476/5815235/eb8093d14b1e/12929_2018_414_Fig1_HTML.jpg

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