Evidence for Host-Bacterial Co-evolution via Genome Sequence Analysis of 480 Thai Mycobacterium tuberculosis Lineage 1 Isolates

Prasit Palittapongarnpim,Wuthiwat Ruengchai,P Palittapongarnpim ,Tada Juthayothin,Norio Yamada,Taane G Clark,Julian Parkhill,Martin L Hibberd,Hideki Yanai,Pacharee Kantipong,Pravech Ajawatanawong,Wasna Viratyosin,Supalert Nedsuwan,Licht Toyo-Oka,Boonchai Chaiyasirinroje,Surakameth Mahasirimongkol,Sissades Tongsima,Jody Phelan,Areeya Disratthakit,Worarat Imasanguan,Jiraporn Wongyai,Nat Smittipat,Katsushi Tokunaga

doi:10.1038/s41598-018-29986-3

Abstract

Tuberculosis presents a global health challenge. Mycobacterium tuberculosis is divided into several lineages, each with a different geographical distribution. M. tuberculosis lineage 1 (L1) is common in the high-burden areas in East Africa and Southeast Asia. Although the founder effect contributes significantly to the phylogeographic profile, co-evolution between the host and M. tuberculosis may also play a role. Here, we reported the genomic analysis of 480 L1 isolates from patients in northern Thailand. The studied bacterial population was genetically diverse, allowing the identification of a total of 18 sublineages distributed into three major clades. The majority of isolates belonged to L1.1 followed by L1.2.1 and L1.2.2. Comparison of the single nucleotide variant (SNV) phylogenetic tree and the clades defined by spoligotyping revealed some monophyletic clades representing EAI2_MNL, EAI2_NTM and EAI6_BGD1 spoligotypes. Our work demonstrates that ambiguity in spoligotype assignment could be partially resolved if the entire DR region is investigated. Using the information to map L1 diversity across Southeast Asia highlighted differences in the dominant strain-types in each individual country, despite extensive interactions between populations over time. This finding supported the hypothesis that there is co-evolution between the bacteria and the host, and have implications for tuberculosis disease control.

Highlights

M. tuberculosis lineages strongly associate with the geographic location, ethnicity and ages of the hosts[2], which could be due to the founder effect or co-adaptation between the bacterial and host population, favouring their stable coexistence[3,4]
The resulting sublineages were compared to the sequences of the Direct Repeat (DR) region obtained from WGS and examined by spoligotyping
The DR region contains a maximum of 69 DR sequences, interposed by 68 Direct Variable Repeats (DVRs)

Summary

Introduction

M. tuberculosis lineages strongly associate with the geographic location, ethnicity and ages of the hosts[2], which could be due to the founder effect or co-adaptation between the bacterial and host population, favouring their stable coexistence[3,4]. The latter hypothesis was supported by the sympatric association between bacterial lineages and patients’ origins[5] which was weakened in HIV-infected patients[6]. Studies of L1 are essential for the End TB strategy[24] It is endemic in 11 of 30 high- burden countries.

Methods

Results

Conclusion