| Autor: |
Worakitchanon, Wittawin, Yanai, Hideki, Piboonsiri, Pundharika, Miyahara, Reiko, Nedsuwan, Supalert, Imsanguan, Worarat, Chaiyasirinroje, Boonchai, Sawaengdee, Waritta, Wattanapokayakit, Sukanya, Wichukchinda, Nuanjan, Omae, Yosuke, Palittapongarnpim, Prasit, Tokunaga, Katsushi, Mahasirimongkol, Surakameth, Fujimoto, Akihiro |
| Zdroj: |
Cell Host & Microbe; Nov2024, Vol. 32 Issue 11, p1972-19198, 17227p |
| Abstrakt: |
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. [Display omitted] • A comprehensive variant analysis across 1,960 Mtb clinical isolates was performed • Mtb genomes are enriched with partially deleterious mutations • GWAS analysis identified eccB2 as being significantly associated with patient prognosis • GWAS analysis of antibiotic resistance associations identified 23 non-canonical genes Accumulation of genetic variations including large-sized mutations in Mycobacterium tuberculosis 's genes associated with tuberculosis patient outcomes and bacterial antibiotic resistance ability. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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