%0 Journal Article %A Nguyen Thi Le Hang %A Minako Hijikata %A Shinji Maeda %A Akiko Miyabayashi %A Shintaro Seto %A Nguyen Thi Kieu Diem %A Nguyen Thi Thanh Yen %A Pham Huu Thuong %A Hoang Van Huan %A Nguyen Phuong Hoang %A Satoshi Mitarai %A Seiya Kato %A Naoto Keicho %T Genomic factors associated with katG-S315T in Mycobacterium tuberculosis clinical isolates in Vietnam %D 2020 %R 10.1183/13993003.congress-2020.5297 %J European Respiratory Journal %P 5297 %V 56 %N suppl 64 %X 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.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 5297.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). %U