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从德国囊性纤维化患者中分离出的脓肿分枝杆菌的分子流行病学研究。

Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients.

机构信息

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.

German Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.

出版信息

Microbiol Spectr. 2022 Aug 31;10(4):e0171422. doi: 10.1128/spectrum.01714-22. Epub 2022 Aug 8.

Abstract

Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among CF patients have been described. To elucidate the epidemiological situation of M. abscessus among CF patients in Germany and to put these data into a global context, we performed whole-genome sequencing of a set of 154 M. abscessus isolates from 123 German patients treated in 14 CF centers. We used MTBseq pipeline to identify clusters of closely related isolates and correlate those with global findings. Genotypic drug susceptibility for macrolides and aminoglycosides was assessed by characterization of the (41), and genes. By this approach, we could identify representatives of all major DCCs (Absc 1, Absc 2, and Mass 1) in our cohort. Intrapersonal isolates showed higher genetic relatedness than interpersonal isolates (median 3 SNPs versus 16 SNPs;  < 0.001). We further identified four clusters with German patients from same centers clustering with less than 25 SNPs distance (range 3 to 18 SNPs) but did not find any hint for in-hospital person-to-person transmission. This is the largest study investigating phylogenetic relations of M. abscessus isolates in Germany. We identified representatives of all reported DCCs but evidence for nosocomial transmission remained inconclusive. Thus, the occurrence of genetically closely related isolates of M. abscessus has to be interpreted with care, as a direct interhuman transmission cannot be directly deduced. Mycobacterium abscessus is a major respiratory pathogen in cystic fibrosis (CF) patients. Recently it has been shown that dominant global clonal complexes (DCCs) have spread worldwide among CF patients. This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing (WGS) of a set of 154 M. abscessus from 123 German patients treated in 14 CF centers. This is the largest study investigating the phylogenetic relationship of M. abscessus CF isolates in Germany.

摘要

脓肿分枝杆菌感染是囊性纤维化 (CF) 患者死亡和发病的主要原因。此外,脓肿分枝杆菌已被怀疑参与人与人之间的传播。2016 年,已描述了在 CF 患者中全球范围内发生的主要克隆复合体 (DCC)。为了阐明德国 CF 患者中脓肿分枝杆菌的流行病学情况,并将这些数据置于全球背景下,我们对来自 14 个 CF 中心的 123 名德国患者的 154 株脓肿分枝杆菌分离株进行了全基因组测序。我们使用 MTBseq 管道来识别密切相关分离株的聚类,并将这些聚类与全球研究结果相关联。通过对 (41)、和 基因进行特征分析,评估大环内酯类和氨基糖苷类药物的基因型药物敏感性。通过这种方法,我们可以在我们的队列中鉴定出所有主要 DCC (Absc 1、Absc 2 和 Mass 1) 的代表。个体内分离株的遗传相关性高于个体间分离株 (中位数 3 个 SNP 与 16 个 SNP;<0.001)。我们进一步确定了来自同一中心的具有德国患者的四个聚类,它们之间的聚类距离小于 25 个 SNP(范围 3 到 18 个 SNP),但没有发现任何院内人与人之间传播的迹象。这是德国最大的一项研究脓肿分枝杆菌分离株的系统发育关系。我们鉴定了所有报告的 DCC 的代表,但医院感染传播的证据仍不确定。因此,必须谨慎解释脓肿分枝杆菌遗传上密切相关的分离株的出现,因为不能直接推断直接的人际传播。脓肿分枝杆菌是囊性纤维化 (CF) 患者的主要呼吸道病原体。最近表明,主要的全球克隆复合体 (DCC) 已在全球范围内在 CF 患者中传播。本研究通过对来自 14 个 CF 中心的 123 名德国患者的 154 株脓肿分枝杆菌进行全基因组测序 (WGS),研究了德国 CF 患者中脓肿分枝杆菌的流行情况。这是德国最大的一项研究脓肿分枝杆菌 CF 分离株的系统发育关系的研究。

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