Emergence of multidrug-resistant Mycobacterium tuberculosis of the Beijing lineage in Portugal and Guinea-Bissau: a snapshot of moving clones by whole-genome sequencing

Abstract
The Beijing genotype comprises a highly disseminated strain type that is frequently associated with multidrug resistant (MDR) tuberculosis (TB) and increased transmissibility but, countries such as Portugal and Guinea-Bissau fall outside the regions phylogeographically associated with this specific genotype. Nevertheless, recent data shows that this genotype might be gradually emerging in these two countries as an underlying cause of primary MDR-TB. Here, we describe the emergence of Mycobacterium tuberculosis Beijing strains associated with MDR-TB in Portugal and Guinea-Bissau demonstrating the presence of the well described superclusters 100-32 and 94-32 in Portugal and Guinea-Bissau, respectively. Genome-wide analysis and comparison with a global genomic dataset of M. tuberculosis Beijing strains, revealed the presence of two genomic clusters encompassing isolates from Portugal and Guinea-Bissau, GC1 (n = 121) and GC2 (n = 39), both of which bore SNP signatures compatible with the 100-32/B0/W148 and 94-32/Central Asia Outbreak clades, respectively. Moreover, GC2 encompasses a cross-border cluster between Portugal, Guinea-Bissau and Brazil thus supporting migration-associated introduction of MDR-TB and subsequent clonal expansion at the community-level. The comparison with global Beijing datasets demonstrates the global reach of the disease and its complex dissemination across multiple countries while in parallel there are clear microevolutionary trajectories towards extensively drug resistant TB.

Citation
Perdigão, J., Silva, C., Maltez, F., Machado, D., Miranda, A., Couto, I., … Portugal, I. (2020). Emergence of multidrug-resistant Mycobacterium tuberculosis of the Beijing lineage in Portugal and Guinea-Bissau: a snapshot of moving clones by whole-genome sequencing. Emerging Microbes & Infections, 9(1), 1342–1353. doi:10.1080/22221751.2020.1774425

Acknowledgements
Financial support was provided by the European Society of Clinical Microbiology and Infectious Diseases, for which we would like to would like to acknowledge the Study Group for Mycobacterial Infections. This study was supported in part by UID/DTP/04138/2019 from Fundação para a Ciência e Tecnologia (FCT), Portugal. DM, IC and MV work was funded by project PTDC/BIA-MIC/30692/2017 and the Global Health and Tropical Medicine (GHTM) Research Center (Grant UID/Multi/04413/2013) from FCT. JP [CEECIND/00394/2017] and DM are supported by FCT through Estímulo Individual ao Emprego Científico. AP was supported by a faculty baseline funding from KAUST [BAS/1/1020-01-01]. IM was supported by Russian Science Foundation (grant 19-14-00013). DM, IC and MV are thankful to projects “ForDILAB-TB” and “A implementação de um novo método de identificação rápida do complexo M. tuberculosis nos Laboratórios de Referência da Tuberculose de Maputo e Beira” from Fundação Calouste Gulbenkian and the Community of the Portuguese Speaking Countries (CPLP). TGC received funding from the MRC UK (Grant no. MR/K000551/1, MR/M01360X/1, MR/N010469/1, MR/R020973/1, MR/R025576/1, MR/S01988X/1, MR/S03563X/1) and BBSRC UK (BB/R013063/1). SC and MH received funding from the Medical Research Council UK grants (MR/R020973/1, MR/R025576/1, MR/S01988X/1, MR/S03563X/1) and the BBSRC UK (BB/R013063/1). JPh is funded by the Medical Research Council UK grants (MR/S03563X/1).

Publisher
Informa UK Limited

Journal
Emerging Microbes & Infections

DOI
10.1080/22221751.2020.1774425

Additional Links
https://www.tandfonline.com/doi/full/10.1080/22221751.2020.1774425

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