Clonal expansion across the seas as seen through CPLP-TB database: A joint effort in cataloguing Mycobacterium tuberculosis genetic diversity in Portuguese-speaking countries
Reis, Ana J.
Scaini, João L.
Silva, Ana B.
e Silva, José Lapa
Clark, Taane G.
von Groll, Andrea
Dalla-Costa, Elis R.
Rossetti, Maria Lúcia
da Silva, Pedro E.A.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Pathogen Genomics Laboratory
KAUST Grant NumberBAS/1/1020-01-01
Online Publication Date2018-03-18
Print Publication Date2018-03
Permanent link to this recordhttp://hdl.handle.net/10754/627361
MetadataShow full item record
AbstractTuberculosis (TB) remains a major health problem within the Community of Portuguese Language Speaking Countries (CPLP). Despite the marked variation in TB incidence across its member-states and continued human migratory flux between countries, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and strain circulation between the countries still exists. To address this, we have assembled and analysed the largest CPLP M. tuberculosis molecular and drug susceptibility dataset, comprised by a total of 1447 clinical isolates, including 423 multidrug-resistant isolates, from five CPLP countries. The data herein presented reinforces Latin American and Mediterranean (LAM) strains as the hallmark of M. tuberculosis populational structure in the CPLP coupled with country-specific differential prevalence of minor clades. Moreover, using high-resolution typing by 24-loci MIRU-VNTR, six cross-border genetic clusters were detected, thus supporting recent clonal expansion across the Lusophone space.To make this data available to the scientific community and public health authorities we developed CPLP-TB (available at http://cplp-tb.ff.ulisboa.pt), an online database coupled with web-based tools for exploratory data analysis. As a public health tool, it is expected to contribute to improved knowledge on the M. tuberculosis population structure and strain circulation within the CPLP, thus supporting the risk assessment of strain-specific trends.
CitationPerdigão J, Silva C, Diniz J, Pereira C, Machado D, et al. (2018) Clonal expansion across the seas as seen through CPLP-TB database: A joint effort in cataloguing Mycobacterium tuberculosis genetic diversity in Portuguese-speaking countries. Infection, Genetics and Evolution. Available: http://dx.doi.org/10.1016/j.meegid.2018.03.011.
SponsorsFinancial 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; Fundação CAPES [PVE-CAPES. 88881.064961/2014-01- Jose R. Lapa e Silva/UFRJ coordinator]; Genotyping and susceptibility profile of Mycobacterium tuberculosis clinical isolates from Rio Grande, Brazil were funded by Apoio a Projetos de Pesquisa em Doenças Negligenciadas, Brazil/MCTI/CNPq/MS-SCTIE – Decit [404081/2012-6] and by Programa Pesquisa para o SUS – PPSUS - FAPERGS/MS/CNPq/SESRS [1193-2551/13-6]; MIRU-VNTR typing and spoligotyping of Mycobacterium tuberculosis clinical isolates from Porto Alegre, Brazil were funded by National Council of Research [CNPq/MCTI/Universal - Project number: 441499/2014-7]; Fundação para a Ciência e a Tecnologia (FCT) Portugal [PTDC/SAU-EPI/122400/2010], part of the EDCTP2 program supported by the European Union; Fundação Calouste Gulbenkian, Portugal [Project ref. P-99934]. JP was supported by a post doc fellowship from project [PTDC/SAU-EPI/122400/2010] and by fellowship [SFRH/BPD/95406/2013] from FCT. The phylogenetic analysis work at Nalin Rastogi's lab was supported by a FEDER grant financed by the European Union and Guadeloupe Region (Programme Opérationnel FEDER-Guadeloupe-Conseil Régional 2014-2020, Grant number 2015-FED-192). IM was supported by Russian Science Foundation (grant 14-14-00292). AP was supported by a faculty baseline funding from KAUST [BAS/1/1020-01-01]. DM was supported by FCT fellowship [SFRH/BPD/100688/2014] and DM, IC MV are thankful to [GHTM UID/Multi/04413/20139] from FCT and 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). CS was supported by FCT [SFRH/BD/73579/2010]. TC is funded by the Medical Research Council UK (Grant no. MR/K000551/1 and MR/M01360X/1, MR/N010469/1, MC_PC_15103).
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Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymersLima, Igo T.; Risko, Chad; Aziz, Saadullah Gary; Da Silva Filho, Demétrio A Da Silva; Bredas, Jean-Luc (J. Mater. Chem. C, Royal Society of Chemistry (RSC), 2014) [Article]Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.
Genomic diversity of drug-resistant Mycobacterium tuberculosis isolates in Lisbon Portugal: Towards tuberculosis genomic epidemiologyPerdigão, João; Silva, Hugo; Machado, Diana; Macedo, Rita; Maltez, Fernando; Silva, Carla; Jordao, Luisa; Couto, Isabel; Mallard, Kim; Coll, Francesc; Hill-Cawthorne, Grant A.; McNerney, Ruth; Pain, Arnab; Clark, Taane G.; Viveiros, Miguel; Portugal, Isabel (International Journal of Mycobacteriology, Medknow, 2015-03) [Abstract]Multidrug- (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) present a challenge to disease control and elimination goals. Lisbon, Portugal, has a high TB incidence rate and unusual and successful XDR-TB strains that have been found in circulation for almost two decades. For the last 20. years, a continued circulation of two phylogenetic clades, Lisboa3 and Q1, which are highly associated with MDR and XDR, have been observed. In recent years, these strains have been well characterized regarding the molecular basis of drug resistance and have been inclusively subjected to whole genome sequencing (WGS). Researchers have been studying the genomic diversity of strains circulating in Lisbon and its genomic determinants through cutting-edge next generation sequencing. An enormous amount of whole genome sequence data are now available for the most prevalent and clinically relevant strains circulating in Lisbon.It is the persistence, prevalence and rapid evolution towards drug resistance that has prompted researchers to investigate the properties of these strains at the genomic level and in the future at a global transcriptomic level. Seventy Mycobacterium tuberculosis (MTB) isolates, mostly recovered in Lisbon, were genotyped by 24-. loci Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeats (MIRU-VNTR) and the genomes sequenced using a next generation sequencing platform - Illumina HiSeq 2000.The genotyping data revealed three major clusters associated with MDR-TB (Lisboa3-A, Lisboa3-B and Q1), two of which are associated with XDR-TB (Lisboa3-B and Q1), whilst the genomic data contributed to elucidating the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of MTB clinical isolates, revealed two major clades responsible for MDR/XDR-TB in the region: Lisboa3 and Q1. The data presented by this study contributes to the expanding knowledge of MTB genomic diversity yielding insights on microevolution and identification of novel compensatory mutations. Additionally, the analysis of non-synonymous/synonymous ratios revealed heterogeneities across the chromosome, genotype and Clusters of Orthologous Groups, highlighting possible and different evolution strategies. Overall, the results that are presented support the notion of an increasing genomic diversity that may support both setting and host adaptation.
Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant settingPerdigão, João; Silva, Hugo; Machado, Diana; Macedo, Rita; Maltez, Fernando; Silva, Carla; Jordao, Luisa; Couto, Isabel; Mallard, Kim; Coll, Francesc; Hill-Cawthorne, Grant A.; McNerney, Ruth; Pain, Arnab; Clark, Taane G.; Viveiros, Miguel; Portugal, Isabel (BMC Genomics, Springer Nature, 2014-11-18) [Article]Background Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. Results In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, two of which are associated with XDR-TB. Whilst the genomic data contributed to elucidate the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of Mycobacterium tuberculosis clinical isolates, revealed two major clades responsible for M/XDR-TB in the region: Lisboa3 and Q1 (LAM). The data presented by this study yielded insights on microevolution and identification of novel compensatory mutations associated with rifampicin resistance in rpoB and rpoC. The screening for other structural variations revealed putative clade-defining variants. One deletion in PPE41, found among Lisboa3 isolates, is proposed to contribute to immune evasion and as a selective advantage. Insertion sequence (IS) mapping has also demonstrated the role of IS6110 as a major driver in mycobacterial evolution by affecting gene integrity and regulation. Conclusions Globally, this study contributes with novel genome-wide phylogenetic data and has led to the identification of new genomic variants that support the notion of a growing genomic diversity facing both setting and host adaptation.