Phylogenomic analysis supports Mycobacterium tuberculosis transmission between humans and elephants

Rajesh Man Rajbhandari; Rajindra Napit; Prajwol Manandhar; Roji Raut; Anupama Gurung; Ajit Poudel; Nisha Shrestha; Amir Sadaula; Dibesh Karmacharya; Christian Gortázar; Paulo Célio Alves; José de la Fuente; João Queirós

doi:10.3389/fvets.2023.1133823

Phylogenomic analysis supports Mycobacterium tuberculosis transmission between humans and elephants

Front Vet Sci. 2023 May 26:10:1133823. doi: 10.3389/fvets.2023.1133823. eCollection 2023.

Authors

Rajesh Man Rajbhandari^{1

2

3

4}, Rajindra Napit⁴, Prajwol Manandhar⁴, Roji Raut⁴, Anupama Gurung⁴, Ajit Poudel⁴, Nisha Shrestha⁴, Amir Sadaula⁵, Dibesh Karmacharya^{4

6}, Christian Gortázar³, Paulo Célio Alves^{1

2

7}, José de la Fuente^{3

8}, João Queirós^{1

2

7}

Affiliations

¹ Departamento de Biologia, Faculdade de Ciencias da Universidade do Porto, Porto, Portugal.
² CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado-BIOPOLIS Program in Genomics, Biodiversity and Land Planning, Campus de Vairão, Universidade do Porto, Vairão, Portugal.
³ SaBio, Instituto de Investigación en Recursos Cinegéticos, IREC (UCLM and CSIC), Ciudad Real, Spain.
⁴ Center for Molecular Dynamics Nepal, Kathmandu, Nepal.
⁵ National Trust for Nature Conservation, Biodiversity Conservation Center, Chitwan, Nepal.
⁶ School of Biological Sciences, Faculty of Science, The University of Queensland, Brisbane, QLD, Australia.
⁷ EBM, Estação Biológica de Mértola, Praça Luís de Camões, Mértola, Portugal.
⁸ Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States.

Abstract

Introduction: Tuberculosis is an infectious disease caused by a group of acid-fast bacilli known as Mycobacterium tuberculosis complex (MTC), which has a major impact on humans. Transmission of MTC across the human-animal interface has been demonstrated by several studies. However, the reverse zoonotic transmission from humans to animals (zooanthroponosis) has often been neglected.

Methods: In this study, we used Nanopore MinION and Illumina MiSeq approaches to sequence the whole genome of M. tuberculosis strains isolated from two deceased Asian elephants (Elephas maximus) and one human in Chitwan, Nepal. The evolutionary relationships and drug resistance capacity of these strains were assessed using the whole genome data generated by the stand-alone tool Tb-Profiler. Phylogenomic trees were also constructed using a non-synonymous SNP alignment of 2,596 bp, including 94 whole genome sequences representative of the previously described M. tuberculosis lineages from elephants worldwide (lineages 1 and 4) and from humans in Nepal (lineages 1, 2 and 3).

Results and discussion: The new genomes achieved an average coverage of 99.6%, with an average depth of 55.67x. These M. tuberculosis strains belong to lineage 1 (elephant DG), lineage 2 (elephant PK) and lineage 4 (human), and none of them were found to have drug-resistant variants. The elephant-derived isolates were evolutionarily closely related to human-derived isolates previously described in Nepal, both in lineages 1 and 2, providing additional support for zooanthroponosis or bidirectional transmission between humans and elephants. The human-derived isolate clustered together with other published human isolates from Argentina, Russia and the United Kingdom in the lineage 4 clade. This complex multi-pathogen, multi-host system is challenging and highlights the need for a One Health approach to tuberculosis prevention and control at human-animal interface, particularly in regions where human tuberculosis is highly endemic.

Keywords: Elephas maximus; one health; tuberculosis; whole-genome sequencing; zooanthroponosis.