{"title":"结核分枝杆菌基因组综合分析揭示了细菌毒力的遗传变异","authors":"Wittawin Worakitchanon, Hideki Yanai, Pundharika Piboonsiri, Reiko Miyahara, Supalert Nedsuwan, Worarat Imsanguan, Boonchai Chaiyasirinroje, Waritta Sawaengdee, Sukanya Wattanapokayakit, Nuanjan Wichukchinda, Yosuke Omae, Prasit Palittapongarnpim, Katsushi Tokunaga, Surakameth Mahasirimongkol, Akihiro Fujimoto","doi":"10.1016/j.chom.2024.10.004","DOIUrl":null,"url":null,"abstract":"Tuberculosis, a disease caused by <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 <em>Mtb</em> clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that <em>Mtb</em> genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in <em>eccB2</em> significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of <em>Rv1216c</em>, <em>Rv1217c</em>, <em>fadD11</em>, and <em>ctpD</em>. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":20.6000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence\",\"authors\":\"Wittawin Worakitchanon, Hideki Yanai, Pundharika Piboonsiri, Reiko Miyahara, Supalert Nedsuwan, Worarat Imsanguan, Boonchai Chaiyasirinroje, Waritta Sawaengdee, Sukanya Wattanapokayakit, Nuanjan Wichukchinda, Yosuke Omae, Prasit Palittapongarnpim, Katsushi Tokunaga, Surakameth Mahasirimongkol, Akihiro Fujimoto\",\"doi\":\"10.1016/j.chom.2024.10.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Tuberculosis, a disease caused by <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 <em>Mtb</em> clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that <em>Mtb</em> genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in <em>eccB2</em> significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of <em>Rv1216c</em>, <em>Rv1217c</em>, <em>fadD11</em>, and <em>ctpD</em>. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.\",\"PeriodicalId\":9693,\"journal\":{\"name\":\"Cell host & microbe\",\"volume\":\"35 1\",\"pages\":\"\"},\"PeriodicalIF\":20.6000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell host & microbe\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.chom.2024.10.004\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell host & microbe","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.chom.2024.10.004","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence
Tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 Mtb clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that Mtb genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in eccB2 significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of Rv1216c, Rv1217c, fadD11, and ctpD. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.
期刊介绍:
Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.