复合分枝杆菌的临床和基因组特征:一项欧洲多国研究。

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Nils Wetzstein, Margo Diricks, Thomas B Anton, Sönke Andres, Martin Kuhns, Thomas A Kohl, Carsten Schwarz, Astrid Lewin, Jan Kehrmann, Barbara C Kahl, Annika Schmidt, Stefan Zimmermann, Moritz K Jansson, Sophie A Baron, Bettina Schulthess, Michael Hogardt, Inna Friesen, Stefan Niemann, Thomas A Wichelhaus
{"title":"复合分枝杆菌的临床和基因组特征:一项欧洲多国研究。","authors":"Nils Wetzstein, Margo Diricks, Thomas B Anton, Sönke Andres, Martin Kuhns, Thomas A Kohl, Carsten Schwarz, Astrid Lewin, Jan Kehrmann, Barbara C Kahl, Annika Schmidt, Stefan Zimmermann, Moritz K Jansson, Sophie A Baron, Bettina Schulthess, Michael Hogardt, Inna Friesen, Stefan Niemann, Thomas A Wichelhaus","doi":"10.1186/s13073-024-01359-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated.</p><p><strong>Methods: </strong>Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort.</p><p><strong>Results: </strong>Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04-0.28, p < 0.001 and OR 0.11 95% CI 0.02-0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%).</p><p><strong>Conclusions: </strong>This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"16 1","pages":"86"},"PeriodicalIF":10.4000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232273/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical and genomic features of Mycobacterium avium complex: a multi-national European study.\",\"authors\":\"Nils Wetzstein, Margo Diricks, Thomas B Anton, Sönke Andres, Martin Kuhns, Thomas A Kohl, Carsten Schwarz, Astrid Lewin, Jan Kehrmann, Barbara C Kahl, Annika Schmidt, Stefan Zimmermann, Moritz K Jansson, Sophie A Baron, Bettina Schulthess, Michael Hogardt, Inna Friesen, Stefan Niemann, Thomas A Wichelhaus\",\"doi\":\"10.1186/s13073-024-01359-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated.</p><p><strong>Methods: </strong>Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort.</p><p><strong>Results: </strong>Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04-0.28, p < 0.001 and OR 0.11 95% CI 0.02-0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%).</p><p><strong>Conclusions: </strong>This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.</p>\",\"PeriodicalId\":12645,\"journal\":{\"name\":\"Genome Medicine\",\"volume\":\"16 1\",\"pages\":\"86\"},\"PeriodicalIF\":10.4000,\"publicationDate\":\"2024-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232273/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genome Medicine\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13073-024-01359-8\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome Medicine","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13073-024-01359-8","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

背景:分枝杆菌复合体(MAC)是中欧最常见的非结核分枝杆菌(NTM),目前包括 12 个物种。阿维分枝杆菌(MAV)、细胞内分枝杆菌细胞内亚种(MINT)和细胞内分枝杆菌奇美拉亚种(MCH)是临床上最常见的分枝杆菌。然而,与潜在病理生物学差异相关的 MAC 种群结构和基因组图谱仍鲜有研究:方法:对来自德国、法国和瑞士的多国 MAC 分离物进行了全基因组测序(WGS)。进行了系统发育分析,并根据 WGS 数据预测了质粒、抗性和毒力基因。数据与公开序列一起被置于全球背景下。最后,将该群体中一部分人的详细临床特征与基因组数据联系起来:结果:总共纳入了来自 465 名患者的 610 个分离株。大多数可归入 MAV(386 个)、MCH(111 个)和 MINT(77 个)。我们证明,在所有主要的 MAC 物种中,从不同患者分离的分离株之间的 SNPs 间距小于 12 个,并且在与 1307 个公开序列进行比对时,可识别出跨欧洲甚至跨大陆的集群。然而,我们的 MCH 分离物中没有一个与加热器-冷却器装置爆发菌株 Zuerich-1 紧密聚类。在 MAV(325/1076,30.2%)、MINT(62/327,19.0%)和几乎所有 MCH 分离物(457/463,98.7%)中都检测到了已知质粒。对氨基糖苷类或大环内酯类药物产生耐药性的情况很少见。总体而言,系统基因组分组与临床表现之间没有直接联系,但在肺外疾病患者中很少发现 MCH 和 MINT(OR 0.12 95% CI 0.04-0.28,p 结论:该研究表明,MCH 和 MINT 的系统基因组分组与临床表现之间没有直接联系,但在肺外疾病患者中很少发现 MCH 和 MINT:这项研究表明,在欧洲和全球范围内,大部分 MAC 分离物中都存在质粒。今后的研究急需确定 MAC 分离物的潜在传播途径以及质粒在毒力中的潜在参与。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical and genomic features of Mycobacterium avium complex: a multi-national European study.

Background: The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated.

Methods: Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort.

Results: Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04-0.28, p < 0.001 and OR 0.11 95% CI 0.02-0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%).

Conclusions: This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信