RT Journal Article
SR Electronic
T1 Genomic factors associated with katG-S315T in Mycobacterium tuberculosis clinical isolates in Vietnam
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 5297
DO 10.1183/13993003.congress-2020.5297
VO 56
IS suppl 64
A1 Nguyen Thi Le Hang
A1 Minako Hijikata
A1 Shinji Maeda
A1 Akiko Miyabayashi
A1 Shintaro Seto
A1 Nguyen Thi Kieu Diem
A1 Nguyen Thi Thanh Yen
A1 Pham Huu Thuong
A1 Hoang Van Huan
A1 Nguyen Phuong Hoang
A1 Satoshi Mitarai
A1 Seiya Kato
A1 Naoto Keicho
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/5297.abstract
AB 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).