| Autor: |
Nguyen Phuong Hoang, Satoshi Mitarai, Nguyen Thi Kieu Diem, Shinji Maeda, Hoang Van Huan, Pham Huu Thuong, Naoto Keicho, Shintaro Seto, Nguyen Thi Le Hang, Nguyen Thi Thanh Yen, Minako Hijikata, Seiya Kato, Akiko Miyabayashi |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Tuberculosis. |
| DOI: |
10.1183/13993003.congress-2020.5297 |
| Popis: |
Background: Isoniazid (INH)-resistant tuberculosis (TB) could seriously affect the fight against TB. We investigated genomic factors that may be associated with katG-S315T, a major INH-resistance conferring mutation, in two large cities of Vietnam. Methods:Mycobacterium tuberculosis (Mtb) isolates were collected from patients with smear-positive pulmonary TB living in two different geographical areas of Vietnam; one in the central and the other in the northern area. Whole genome sequencing was performed using an Illumina MiSeq platform. Major drug resistance-conferring mutations were extracted with the TB-Profiler tool. Using a bacterial genome-wide approach based on linear mixed models, we investigated associations between 31-bp k-mers and Mtb isolates harboring katG-S315T in each cohort, and then compared them. Results: Genome sequences were obtained from 181 Mtb isolates in the central and 322 in the northern area. Isolates with katG-S315T accounted for 12.7% and 26.2% respectively. Ten genes harboring k-mers significantly associated with the katG-S315T phenotype were shared by the two cohorts. Genomic variants responsible for these k-mers of all these genes also showed significant associations with the S315T mutation, when a variant-based approach was conducted. A deletion-based analysis also identified several significant genes, including esxD with a 324-bp deletion and PE_PGRS30 with 109-bp deletion in the central-area cohort. Conclusions: We demonstrated that several genomic variations of the pathogen are associated with katG-S315T in common, and these genomic factors may be related to the low fitness cost of INH-resistant strains in Vietnam. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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