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Projeto de investigação
Center for Innovative Biomedicine and Biotechnology
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Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature
Publication . Fernandes, Ana Filipa; Gonçalves, Luís Gafeira; Bento, Maria; Anjo, Sandra I.; Manadas, Bruno; Barroso, Clara; Villar, Miguel; Macedo, Rita; Simões, Maria João; Coelho, Ana Varela
Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups-healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.
Mycobacterium appelbergii sp. nov., a Novel Species Isolated from a Drinking Water Fountain in a Rural Community
Publication . Roxo, Inês Cravo; Alarico, Susana; Fonseca, Ana; Machado, Daniela; Maranha, Ana; Tiago, Igor; Duarte, Raquel; Empadinhas, Nuno
Three isolates of a novel, rapidly growing, non-pigmented Mycobacterium species were recovered from the water and runoff of a public fountain in a rural village in central Portugal, formerly used by the local population as a source of drinking water and not accessible to animals. High-quality draft genome sequencing, in silico DNA–DNA hybridization, and phylogenetic analyses confirmed that isolates 21AC1T, 21AC14, and 21AC21 represent a previously undescribed species within the genus Mycobacterium, forming a distinct phylogenetic lineage closely related to Mycobacterium wolinskyi, Mycobacterium goodii and Mycobacterium smegmatis. MALDI-TOF MS analysis of the type strain 21AC1T revealed a unique spectral profile. A comprehensive polyphasic characterization was performed, including chemotaxonomic analyses of fatty acid and mycolic acid composition, as well as an extensive biochemical characterization. Their susceptibility to 12 antimicrobials was also assessed. The identification and characterization of novel nontuberculous mycobacteria species are of increasing environmental and clinical relevance, as infections by these opportunistic pathogens are on the rise globally. Based on our findings, we propose that isolates 21AC1T, 21AC14, and 21AC21 represent a novel species, for which we propose the name Mycobacterium appelbergii sp. nov., with the type strain designated as 21AC1T (=BCCM/ITM 501212 = DSM 113570) and the additional two strains as 21AC14 (=BCCM/ITM 501447 = DSM 118402) and 21AC21 (=BCCM/ITM 501448 = DSM 118403).
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
6817 - DCRRNI ID
Número da atribuição
UIDP/04539/2020