Phenotypic and genotypic features of the Mycobacterium tuberculosis lineage 1 subgroup in central Vietnam

Nguyen Thi Le Hang,Nguyen Thi Thanh Yen,Shinji Maeda,Pham Huu Thuong,Nguyen Thi Kieu Diem,Akiko Miyabayashi,Le Van Duc,Keiko Wakabayashi,Naoto Keicho,Seiya Kato,Hoang Van Huan,Satoshi Mitarai,Shintaro Seto,Nguyen Phuong Hoang,Minako Hijikata

doi:10.1038/s41598-021-92984-5

Abstract

Mycobacterium tuberculosis (Mtb) has different features depending on different geographic areas. We collected Mtb strains from patients with smear-positive pulmonary tuberculosis in Da Nang, central Vietnam. Using a whole genome sequencing platform, including genome assembly complemented by long-read-sequencing data, genomic characteristics were studied. Of 181 Mtb isolates, predominant Vietnamese EAI4_VNM and EAI4-like spoligotypes (31.5%), ZERO strains (5.0%), and part of EAI5 (11.1%) were included in a lineage-1 (L1) sublineage, i.e., L1.1.1.1. These strains were found less often in younger people, and they genetically clustered less frequently than other modern strains. Patients infected with ZERO strains demonstrated less lung infiltration. A region in RD2bcg spanning six loci, i.e., PE_PGRS35, cfp21, Rv1985c, Rv1986, Rv1987, and erm(37), was deleted in EAI4_VNM, EAI4-like, and ZERO strains, whereas another 118 bp deletion in furA was specific only to ZERO strains. L1.1.1.1-sublineage-specific deletions in PE_PGRS4 and PE_PGRS22 were also identified. RD900, seen in ancestral lineages, was present in majority of the L1 members. All strains without IS6110 (5.0%) had the ZERO spoligo-pattern. Distinctive features of the ancestral L1 strains provide a basis for investigation of the modern versus ancestral Mtb lineages and allow consideration of countermeasures against this heterogeneous pathogen.

Highlights

Mycobacterium tuberculosis (Mtb) has different features depending on different geographic areas
EAI accounted for 42.5% (77/181), which comprised an EAI4_VNM subgroup (57/181 isolates or 31.5%, of which 8/57 were EAI4_VNM-like) and an EAI5 subgroup (20/181 or 11.1%, of which 6/20 were EAI5-like, following the criterion described in the Methods and Materials section)
Our study demonstrated that EAI Mtb strains, especially those of a typical Vietnamese EAI4_VNM and a pattern similar to EAI4_VNM (EAI4_VNM-like), were most frequently observed in Da Nang City and that ZERO strains showing a distinctive spoligo-pattern were genetically closely related to the EAI4 clade in Vietnam

Summary

Introduction

Mycobacterium tuberculosis (Mtb) has different features depending on different geographic areas. Of 181 Mtb isolates, predominant Vietnamese EAI4_VNM and EAI4-like spoligotypes (31.5%), ZERO strains (5.0%), and part of EAI5 (11.1%) were included in a lineage-1 (L1) sublineage, i.e., L1.1.1.1. These strains were found less often in younger people, and they genetically clustered less frequently than other modern strains. A major sublineage of L2, are predominant in the northern and southern regions, whereas EAI strains in L1 are more frequently seen in the central area[14,15,16]. We compared the results with a northern study cohort, another southern cohort studied by others, and reports from other countries

Methods

Results

Conclusion