Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim

Fabrizio Menardo,Hellen Hiza,Qingyun Liu,Levan Jugheli,Daniela Brites,Lujeko Kamwela,Liliana K Rutaihwa,Helen Cox,Christophe Sola,Prasit Palittapongarnpim,Mohamed Sasamalo,Klaus Reither,Voahangy Rasolofo,Moses Joloba,Sebastian M Gygli,Bijaya Malla,Iñaki Comas,Christian Beisel,Julia Feldmann,Niaina Rakotosamimanana,Dorothy Yeboah-Manu,Emilyn Costa Conceição,Rafael Silva Duarte,Surakameth Mahasirimongkol,Horng-Yunn Dou,Janet Fyfe,Jerry Hella,Lukas Fenner,Michaela Zwyer,Serej D Ley,Qian Gao,Miriam Reinhard,Darı́o Garcı́a De Viedma ,Alberto L García‐Basteiro ,Midori Kato‐Maeda ,Philip Noël Suffys ,Mireia Coscollá ,Sònia Borrell ,Chloé Loiseau ,Karla Valéria Batista Lima ,Sébastien Gagneux

doi:10.12688/f1000research.28318.2

Abstract

Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.

Highlights

The global tuberculosis (TB) epidemic is a major public health emergency, disproportionately affecting vulnerable populations and worsening existing inequalities
While L2 and L4 strains occur across the world, Lineage 1 (L1) strains are predominantly found around the rim of the Indian Ocean (East Africa, South Asia, and Southeast Asia)
We screened a large collection of publicly available Mycobacterium tuberculosis complex (MTBC) genome sequences and selected those belonging to L1 and L3

Summary

Introduction

The global tuberculosis (TB) epidemic is a major public health emergency, disproportionately affecting vulnerable populations and worsening existing inequalities. TB is spread worldwide, but not all regions are affected: 95% of new TB cases occur in Africa and Asia, and the eight countries with the largest burden account for two thirds of the total number of cases (WHO, 2020). Human TB is caused by members of the Mycobacterium tuberculosis complex (MTBC), which includes nine phylogenetic lineages with different geographic distributions. Five of these lineages are restricted to Africa (L5, L6, L7, L8, and L9), while the remaining four (L1, L2, L3, L4) are more broadly distributed (Chihota et al, 2018; Coscollá et al, 2021; Gagneux, 2018; Ngabonziza et al, 2020). Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans

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Conclusion