Browsing by Author "Miranda, Anabela"
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- Emergence of multidrug-resistant Mycobacterium tuberculosis of the Beijing lineage in Portugal and Guinea-Bissau: a snapshot of moving clones by whole-genome sequencingPublication . Perdigão, João; Silva, Carla; Maltez, Fernando; Machado, Diana; Miranda, Anabela; Couto, Isabel; Rabna, Paulo; Florez de Sessions, Paola; Phelan, Jody; Pain, Arnab; McNerney, Ruth; Hibberd, Martin L.; Mokrousov, Igor; Clark, Taane G.; Viveiros, Miguel; Portugal, IsabelThe 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.
- Rapid determination of anti-tuberculosis drug resistance from whole-genome sequencesPublication . Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, Mridul; Miranda, Anabela; Alves, Adriana; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Hasan, Zahra; Hasan, Rumina; Glynn, Judith R.; Martin, Nigel; Pain, Arnab; Clark, Taane G.Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online 'TB-Profiler' tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing.
- SNP typing reveals similarity in Mycobacterium tuberculosis genetic diversity between Portugal and Northeast BrazilPublication . Lopes, João S.; Marques, Isabel; Soares, Patricia; Nebenzahl-Guimaraes, Hanna; Costa, João; Miranda, Anabela; Duarte, Raquel; Alves, Adriana; Macedo, Rita; Duarte, Tonya A.; Barbosa, Theolis; Oliveira, Martha; Nery, Joilda S.; Boechat, Neio; Pereira, Susan M.; Barreto, Mauricio L.; Pereira-Leal, José; Gomes, Maria Gabriela Miranda; Penha-Goncalves, CarlosHuman tuberculosis is an infectious disease caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Although spoligotyping and MIRU-VNTR are standard methodologies in MTBC genetic epidemiology, recent studies suggest that Single Nucleotide Polymorphisms (SNP) are advantageous in phylogenetics and strain group/lineages identification. In this work we use a set of 79 SNPs to characterize 1987 MTBC isolates from Portugal and 141 from Northeast Brazil. All Brazilian samples were further characterized using spolygotyping. Phylogenetic analysis against a reference set revealed that about 95% of the isolates in both populations are singly attributed to bacterial lineage 4. Within this lineage, the most frequent strain groups in both Portugal and Brazil are LAM, followed by Haarlem and X. Contrary to these groups, strain group T showed a very different prevalence between Portugal (10%) and Brazil (1.5%). Spoligotype identification shows about 10% of mis-matches compared to the use of SNPs and a little more than 1% of strains unidentifiability. The mis-matches are observed in the most represented groups of our sample set (i.e., LAM and Haarlem) in almost the same proportion. Besides being more accurate in identifying strain groups/lineages, SNP-typing can also provide phylogenetic relationships between strain groups/lineages and, thus, indicate cases showing phylogenetic incongruence. Overall, the use of SNP-typing revealed striking similarities between MTBC populations from Portugal and Brazil.
- Using genomics to understand the origin and dispersion of multidrug and extensively drug resistant tuberculosis in PortugalPublication . Perdigão, João; Gomes, Pedro; Miranda, Anabela; Maltez, Fernando; Machado, Diana; Silva, Carla; Phelan, Jody E.; Brum, Laura; Campino, Susana; Couto, Isabel; Viveiros, Miguel; Clark, Taane G.; Portugal, IsabelPortugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR- and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach.