Browsing by Author "David, Susana"
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- Base genética de suscetibilidade à infeção por SARS-CoV-2, hipótese de abordagem por CGASPublication . David, Susana; Dorado, Guillermo; Bosne, StephanieUma característica importante da pandemia da COVID-19 é a grande variabilidade interindividual na manifestação clínica da infeção, entre doença assintomática, formas graves de doença e morte. Como até à data, as mutações identificadas no SARS-CoV-2 não explicam esta amplitude de manifestações clínicas, a genética do hospedeiro humano ganha aqui uma importância crucial.
- A current guide to candidate gene association studiesPublication . David, SusanaImportant factors contribute to a gained momentum in candidate gene association studies (CGAS) including the generalized use of NGS, growing opportunity for hospital-based research and availability of open-source databases and bioinformatics tools. This report summarizes the general principles and analytical methods as a guide to CGAS in today’s favorable context.
- Determinants of the Sympatric Host-Pathogen Relationship in TuberculosisPublication . David, Susana; Mateus, A.R.A.; Duarte, Elsa; Albuquerque, José Maria; Portugal, Clara; Sancho, Luísa; Lavinha, João; Gonçalves, GuilhermeMajor contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host–pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic haracterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of theprevalence of sympatric and allopatric TB in relation to patients’ age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the EuroAmerican lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants
- Evidência para o efeito de um “gene principal” do hospedeiro na suscetibilidade à tuberculose multirresistente em PortugalPublication . David, Susana; Mateus, Ana R.A.; Duarte, Elsa L.; Albuquerque, José; Portugal, Clara; Sancho, Luísa; Lavinha, João; Gonçalves, GuilhermeA análise do genoma do patógeno e da genética do hospedeiro tem possibilitado o entendimento da coevolução do Mycobacterium tuberculosis com o seu hospedeiro humano, conduzindo a relações simpátricas mais estáveis entre o hospedeiro e o patógeno. A influência de fatores clínicos (coinfeção pelo VIH e tuberculose multirresistente (MDRTB]) e demográficos (sexo e idade) na relação hospedeiro-patógeno simpátrica foi investigada utilizando o spacer oligonucleotide typing (spoligotyping) enquanto método de genotipagem de isolados do M. tuberculosis pertencendo à linhagem Euro-Americana. Foram analisados 547 casos de tuberculose (TB) e os isolados correspondentes, de uma amostragem consecutiva de seis anos num contexto de elevada prevalência para a coinfecção TB-VIH (32,0%). Entre estes, 62,0% resultaram de infeção causada pelos principais genótipos de M. tuberculosis em circulação. A relação simpátrica foi definida de acordo com o spoligotype em comparação com a base de dados internacional de spoligotype SpolDB4. Foi evidenciada uma associação estatisticamente significativa da MDRTB com os isolados simpátricos, independente da coinfeção pelo VIH. Para além disso, o resultado do estudo da prevalência da distribuição da infeção com a idade foi sugestivo de que os determinantes da predisposição genética do hospedeiro à TB simpátrica eram impulsionados por variantes comuns sob efeito de um “gene principal” (“major gene effect ”). Em termos de saúde pública, estes resultados poderão dar um importante contributo para a elaboração de modelos que preveem a duração dos ciclos de transmissão ativa, nomeadamente associada a casos graves de MDRTB.
- Genetic variants in the IFNGR2 locus associated with severe chronic Q feverPublication . David, Susana; Castro, Liliana; Duarte, Elsa; Gaspar, Ulisses; Rodrigues, Maria Rosário da Costa; Cueto-Rojo, Maria Vanessa; Mendonça, Joana; Ferrão, José; Machado, Miguel; Poças, José; Lavinha, João; Vieira, Luís; Santos, Ana Sofia; ElsevierQ fever is a highly contagious zoonosis capable of causing large outbreaks of important health and economic consequences. Host genetic factors are believed to influence the development of severe chronic Q fever following the infection by the etiological agent, Coxiella burnetii. Targetted next generation sequencing (NGS) was performed in a case-control genetic association study on 53 confirmed Q fever cases, including 38 compatible with acute and 15 with chronic disease, and 29 samples from the general Portuguese population. Four SNPs in the IFNGR2 locus, rs78407108 G > A, rs17879956 C > T, rs7277167 C > T, and rs9974603 C > A, showed a statistically significant association to chronic Q fever, resisting the Bonferroni correction. These belonged to haplotypes significantly associated with chronic Q fever. The individual SNPs are referenced in the GTEx database as possible eQTLs. Given the direct bearing of IFNGR2 on IFN-γ signaling, the possible involvement of the associated variants with higher IFNGR2 expression could be in line with observations suggesting that IFN-γ production in chronic Q fever patients is significantly higher than in healthy controls. Further investigations are required to clarify the role of IFNGR2 signaling in association with chronic Q fever.
- Gripe: interação do vírus influenza com o seu hospedeiro humanoPublication . David, SusanaA gripe é responsável por 3 a 5 milhões de casos de doença grave, com 290 000 a 650 000 mortes anuais a nível mundial. A Organização Mundial da Saúde decretou uma prioridade nos estudos sobre o papel da genética do hospedeiro na suscetibilidade a formas clinicamente graves da infeção pelo vírus da influenza.
- Implication of the RDRio Mycobacterium tuberculosis sublineage in multidrug resistant tuberculosis in PortugalPublication . David, Susana; Duarte, Elsa L.; Leite, Clarice Queico Fugimura; Ribeiro, João-Nuno; Maio, José-Nuno; Paixão, Eleonora; Portugal, Clara; Sancho, Luísa; Germano de Sousa, JoséMultidrug and extensively drug resistant Mycobacterium tuberculosis are a threat to tuberculosis control programs. Genotyping methods, such as spoligotyping and MIRU–VNTR typing (Mycobacterial Interspersed Repetitive Units), are useful in monitoring potentially epidemic strains and estimating strain phylogenetic lineages and/or genotypic families. M. tuberculosis Latin American Mediterranean (LAM) family is a major worldwide contributor to tuberculosis (TB). LAM specific molecular markers, Ag85C103 single nucleotide polymorphism (SNP) and RDRio long-sequence polymorphism (LSP), were used to characterize spoligotype signatures from 859 patient isolates from Portugal. LAM strains were found responsible for 57.7% of all tuberculosis cases. Strains with the RDRio deletion (referred to as RDRio) were estimated to represent 1/3 of all the strains and over 60% of the multidrug resistant (MDR) strains. The major spoligotype signature SIT20 belonging to the LAM1 RDRio sublineage, represented close to 1/5th of all the strains, over 20% of which were MDR. Analysis of published datasets according to stipulated 12 loci MIRU–VNTR RDRio signatures revealed that 96.3% (129/134) of MDR and extensively drug resistant (XDR) clusters were RDRio. This is the first report associating the LAM RDRio sublineage with MDR. These results are an important contribution to the monitoring of these strains with heightened transmission for future endeavors to arrest MDR–TB and XDR–TB.
- Isolation and identification of Bacillus strains with antimycobacterial activityPublication . El Guendouzi, Souraya; David, Susana; Mohammed, Hassi; Abdellatif, Haggoud; Saad Ibn, Souda; Abdellah, Houari; Mohammed, IraquiTuberculosis is the principal cause of death worldwide due to an infectious disease. The resurgence of tuberculosis, followed by the increase in prevalence of infections caused by nontuberculous mycobacteria (NTM), as well as the multi-drug resistance of mycobacteria to the majority of currently available antibiotics, have encouraged research for new antimycobacterial agents. Soil and water samples from different Moroccan biotopes, have led to the isolation of four bacterial strains (M, R, G and S), showing an inhibitory effect on mycobacterial growth. This effect was shown to be due to secreted substances in the growth medium. From subsequent analysis it was concluded that these strains produced different active substances. Sequencing of the 16S rRNA showed that these isolates belong to the genus Bacillus. The active substance from isolate M, showed the more important inhibitory effect on mycobacterial growth. It is precipitated with ammonium sulfate and lost all activity when treated with Proteinase K, revealing its protein nature.
- Métodos para estudos populacionais de associação genótipo-fenótipo com base em genes candidatosPublication . David, SusanaOs estudos populacionais de associação genótipo-fenótipo com base em genes candidatos (Candidate gene Association Studies – CGAS) conhecem um recente incremento resultante das abordagens baseadas na sequenciação de nova geração. Este artigo resume os princípios gerais do método CGAS que tem vindo a contribuir para a identificação de variantes genéticas causais e para a nossa compreensão da arquitetura genética das doenças humanas.
- Tuberculosis diagnosis after bleach processing for early stage tuberculosis laboratory capacity buildingPublication . David, Susana; Sutre, Ana Filipa; Sanca, Armando; Mané, Alfredo; Henriques, Victor; Portugal, Clara; Sancho, Luísa; Cardoso, Ana; Paixão, Eleonora; Duarte, Elsa Leclerc; Leite, Clarice Queico Fujimura; Salem, Julia Ignez; Antunes, AbílioThe diagnosis of tuberculosis is seriously hampered in the absence of standard biosafety laboratory facilities for specimen concentration and Mycobacterium tuberculosis culture. Within a laboratory twinning arrangement, heat-fixed direct smear and sediment from 74 bleach-processed and 20 non-processed specimens from Cumura Hospital, Guinea-Bissau, were sent to Lisbon for molecular evaluation of rifampicin resistance. Sequence analysis of a 369 base-pair rpoB locus detected 3.2% (3/94) resistant specimens. To our knowledge, this represents the first report on the molecular analysis of M. tuberculosis from bleach-processed sputum, an alternative to current diagnostic practice in low-resource settings.