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基于线粒体大亚基核糖体 RNA 和二氢叶酸合成酶基因分型的土耳其人群中肺孢子菌分离株的遗传多样性。

Genetic diversity of Pneumocystis jirovecii isolates among Turkish population based on mitochondrial large subunit ribosomal RNA and dihydropteroate synthase gene typing.

机构信息

Department of Medical Parasitology, Dokuz Eylul University Faculty of Medicine, 35340 Izmir, Turkey.

Department of Pulmonary Diseases, Dokuz Eylul University Faculty of Medicine, 35340 Izmir, Turkey.

出版信息

Med Mycol. 2021 Jul 14;59(8):813-820. doi: 10.1093/mmy/myab004.

Abstract

UNLABELLED

Pneumocystis jirovecii (P. jirovecii) is an atypical fungus that can cause severe interstitial pneumonia in immunocompromised patients. In this study, mitochondrial large subunit ribosomal RNA (mtLSU-rRNA) and dihydropteroate synthase (DHPS) gene polymorphism in P. jirovecii isolates were investigated in Western Turkey's Izmir province and its surroundings. For this purpose, a total of 157 P. jirovecii isolates obtained from bronchoalveolar lavage samples of hospitalized cases and lung tissue samples of autopsy cases who died outside hospital were examined. Genotypes were identified by direct sequencing of mtLSU-rRNA restriction fragment length polymorphism analysis of the DHPS gene amplicons. The mtLSU-rRNA analysis revealed that genotype 2 was the most common genotype with 58%. The following genotypes were genotype 3 (13%), genotype 1 (11.6%) and genotype 4 (5.1%), while genotype 5 (0.7%) was detected in only one autopsy case. In addition, 16 (11.6%) cases had dual or triple different genotypes (mixed infection). It was observed that the genotype distribution was not affected by characteristics such as age, gender and immune status. However, the predominance of genotype 2 in solid organ tumors and the predominance of mixed infection in patients with chronic pulmonary disease were statistically significant. On the other hand, DHPS gene amplification was positive in 137 (87.3%) of 157 samples. While no mutation was observed in 135 samples, the association of wild-type and 57th codon mutation was detected in two hospitalized cases (1.5%). In this study, important epidemiological data on the distribution of mtLSU-rRNA genotypes were obtained. Also the existence of DHPS gene mutations associated with potential drug resistance in our community was shown for the first time. Further studies are needed to evaluate the possible effects of genotypes on the prognosis of the disease to help with the clinician's treatment decisions.

LAY ABSTRACT

Pneumocystis jirovecii (P. jirovecii) is an atypical fungus that can cause life-threatening pneumonia in immunocompromised patients. In this study, we investigated the mtLSU-rRNA and DHPS gene polymorphisms in P. jirovecii isolates from both hospital and autopsy cases.

摘要

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卡氏肺孢子菌(P. jirovecii)是一种非典型真菌,可导致免疫功能低下的患者发生严重间质性肺炎。在这项研究中,我们对来自住院患者和院外死亡患者的支气管肺泡灌洗液样本和肺组织样本中的卡氏肺孢子菌分离株的 mtLSU-rRNA 和二氢叶酸合成酶(DHPS)基因多态性进行了研究。通过 mtLSU-rRNA 分析、DHPS 基因扩增子的限制性片段长度多态性分析,直接测序鉴定基因型。mtLSU-rRNA 分析显示,基因型 2 最为常见,占 58%。以下依次为基因型 3(13%)、基因型 1(11.6%)和基因型 4(5.1%),而仅在 1 例尸检病例中检测到基因型 5(0.7%)。此外,16 例(11.6%)病例存在双重或三重不同基因型(混合感染)。观察到基因型分布不受年龄、性别和免疫状态等特征的影响。然而,在实体器官肿瘤中,基因型 2 占主导地位,在慢性肺部疾病患者中,混合感染占主导地位,这具有统计学意义。另一方面,在 157 个样本中,137 个(87.3%)DHPS 基因扩增阳性。在 135 个样本中未观察到突变,在 2 例住院患者中检测到野生型和 57 位密码子突变的关联(1.5%)。本研究获得了关于 mtLSU-rRNA 基因型分布的重要流行病学数据。此外,还首次在本地区发现与潜在药物耐药性相关的 DHPS 基因突变。需要进一步研究以评估基因型对疾病预后的可能影响,以帮助临床医生做出治疗决策。

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