Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence
Issued Date
2024-01-01
Resource Type
ISSN
19313128
eISSN
19346069
Scopus ID
2-s2.0-85207810385
Journal Title
Cell Host and Microbe
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cell Host and Microbe (2024)
Suggested Citation
Worakitchanon W., Yanai H., Piboonsiri P., Miyahara R., Nedsuwan S., Imsanguan W., Chaiyasirinroje B., Sawaengdee W., Wattanapokayakit S., Wichukchinda N., Omae Y., Palittapongarnpim P., Tokunaga K., Mahasirimongkol S., Fujimoto A. Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence. Cell Host and Microbe (2024). doi:10.1016/j.chom.2024.10.004 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101916
Title
Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence
Author's Affiliation
Faculty of Science, Mahidol University
Graduate School of Medicine
National Institute of Infectious Diseases
National Center for Global Health and Medicine
Thailand Ministry of Public Health
The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
TB/HIV Research Foundation (THRF)
Chiangrai Prachanukroh Hospital
Graduate School of Medicine
National Institute of Infectious Diseases
National Center for Global Health and Medicine
Thailand Ministry of Public Health
The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association
TB/HIV Research Foundation (THRF)
Chiangrai Prachanukroh Hospital
Corresponding Author(s)
Other Contributor(s)
Abstract
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.