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对一名反复发生类鼻疽病患者的配对临床分离株进行的比较基因组分析显示,其宿主内突变率较低。

Comparative genomic analysis of paired clinical isolates from a patient with recurrent melioidosis reveals a low within-host mutation rate.

作者信息

Raj Sruthi, Peela Sreeram Chandra Murthy, Kumar Hithesh, Ramaiah Sudha, Sistla Sujatha

机构信息

Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

Present address: Department of Microbiology, Sukh Sagar Medical College, Jabalpur, Madhya Pradesh, India.

出版信息

J Med Microbiol. 2025 Apr;74(4). doi: 10.1099/jmm.0.002003.

DOI:10.1099/jmm.0.002003
PMID:40232806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12282283/
Abstract

Relapse of melioidosis is not uncommon and can occur due to shorter oral antibiotic therapy in the first episode. In such isolates, low mutation rates were identified amongst paired clinical isolates during relapse, but large-scale structural variants were also common. Using pair-wise comparison, a low number of mutations, especially amongst the virulence and antibiotic resistance genes, may be present amongst the paired isolates obtained during the study period. A pair of clinical isolates obtained from a patient with recurrent melioidosis during the study period (January 2018 to June 2021) was analysed for identifying the genomic relatedness and DNA changes that may have caused the relapse. Using paired-end Illumina sequencing, following appropriate data quality checks, the genomes were assembled using Shovill pipeline, whilst the variants were called using Snippy. Structural variants were detected using TIDDIT, and functional associations were identified using the STRING database searches. One of the isolates (from the second episode) had a highly fragmented genome, but very few structural variants and SNPs were identified. Both the isolates had similar virulence and antibiotic resistance genes; however, owing to the few structural changes, a slightly lower number of virulence genes were observed. Together, they shared 99.8% of the proteomes, and most variants identified spanned either hypothetical proteins or un-annotated regions. Based on comprehensive genome analysis the two strains were genetically similar, with a few structural variants, implying the second episode to be a relapse rather than a re-infection. There was no difference in the antibiotic resistance or virulence genes that may have explained the relapse.

摘要

类鼻疽复发并不罕见,可能是由于首次发作时口服抗生素治疗疗程较短所致。在这类分离株中,复发期间配对临床分离株的突变率较低,但大规模结构变异也很常见。通过成对比较,在研究期间获得的配对分离株中可能存在少量突变,尤其是在毒力和抗生素抗性基因中。对一名在研究期间(2018年1月至2021年6月)复发性类鼻疽患者的一对临床分离株进行分析,以确定可能导致复发的基因组相关性和DNA变化。使用双末端Illumina测序,在进行适当的数据质量检查后,使用Shovill流程组装基因组,同时使用Snippy调用变异。使用TIDDIT检测结构变异,并使用STRING数据库搜索识别功能关联。其中一个分离株(来自第二次发作)的基因组高度碎片化,但鉴定出的结构变异和单核苷酸多态性很少。两个分离株都有相似的毒力和抗生素抗性基因;然而,由于结构变化较少,观察到的毒力基因数量略少。它们总共共享99.8%的蛋白质组,鉴定出的大多数变异跨越假设蛋白质或未注释区域。基于全面的基因组分析,这两个菌株在基因上相似,有一些结构变异,这意味着第二次发作是复发而非再次感染。可能解释复发的抗生素抗性或毒力基因没有差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c337/12282283/6d91f2605de9/jmm-74-02003-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c337/12282283/6d91f2605de9/jmm-74-02003-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c337/12282283/5f1675f9a079/jmm-74-02003-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c337/12282283/0bc27da259de/jmm-74-02003-g003.jpg
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本文引用的文献

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Clinical Profile and Predictors of Mortality among Patients with Melioidosis.类鼻疽病患者的临床特征及死亡预测因素
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The Epidemiology of Melioidosis and Its Association with Diabetes Mellitus: A Systematic Review and Meta-Analysis.类鼻疽的流行病学及其与糖尿病的关联:一项系统评价和荟萃分析。
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