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印度单一三级中心患者中肺孢子菌杰氏肺孢子虫的循环基因型及其临床相关性。

Circulating genotypes of Pneumocystis jirovecii and its clinical correlation in patients from a single tertiary center in India.

机构信息

Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.

Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Eur J Clin Microbiol Infect Dis. 2017 Sep;36(9):1635-1641. doi: 10.1007/s10096-017-2977-9. Epub 2017 Apr 11.

Abstract

The present study was carried out with the objectives of genotyping Pneumocystis jirovecii at three distinct loci, to identify the single nucleotide polymorphisms (SNPs), and to study its clinical implications in patients with Pneumocystis pneumonia (PCP). Analysis of genetic diversity in P. jirovecii from immunocompromised patients was carried out by genotyping at three distinct loci encoding mitochondrial large subunit rRNA (mtLSU rRNA), cytochrome b (CYB), and superoxide dismutase (SOD) using polymerase chain reaction (PCR) assays followed by direct DNA sequencing. Of the 300 patients enrolled in the present study, 31 (10.33%) were positive for PCP by a specific mtLSU rRNA nested PCR assay, whereas only 15 P. jirovecii could be amplified at the other two loci (SOD and CYB). These positives were further subjected to sequence typing. Important genotypic combinations between four SNPs (mt85, SOD110, SOD215, and CYB838) and clinical outcomes could be observed in the present study, and mt85A, mt85T, and SOD110C/SOD215T were frequently associated with "negative follow-up". These SNPs were also noted to be relatively more prevalent amongst circulating genotypes in our study population. The present study is the first of its kind from the Indian subcontinent and demonstrated that potential SNPs of P. jirovecii may possibly be attributed to the clinical outcome of PCP episodes in terms of severity or fatality in different susceptible populations likely to develop PCP during their course of illness.

摘要

本研究的目的是对三个不同基因座的肺孢子菌进行基因分型,以确定单核苷酸多态性(SNP),并研究其在肺孢子菌肺炎(PCP)患者中的临床意义。通过聚合酶链反应(PCR)分析对来自免疫功能低下患者的肺孢子菌进行基因分型,以鉴定线粒体大亚基 rRNA(mtLSU rRNA)、细胞色素 b(CYB)和超氧化物歧化酶(SOD)三个不同基因座的遗传多样性,随后直接进行 DNA 测序。在本研究中,对 300 名患者进行了检测,通过特异性 mtLSU rRNA 巢式 PCR 检测,有 31 名(10.33%)患者 PCP 阳性,而其他两个基因座(SOD 和 CYB)只能扩增 15 株肺孢子菌。这些阳性结果进一步进行了序列分型。在本研究中可以观察到四个 SNP(mt85、SOD110、SOD215 和 CYB838)之间的重要基因型组合与临床结局之间存在相关性,并且 mt85A、mt85T 和 SOD110C/SOD215T 与“阴性随访”密切相关。这些 SNP 也在我们研究人群中的循环基因型中相对更为常见。本研究是印度次大陆的首例研究,表明肺孢子菌的潜在 SNP 可能与不同易感人群中 PCP 发作的临床结局(严重程度或死亡率)有关,这些人群在患病过程中可能会发生 PCP。

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