Biotecnologia

Micobacteriologia Molecular e Microbioma

Microbiologia Molecular

Biossíntese

Micobactérias

Metabolitos

Microbioma

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Líder

Nuno Empadinhas

Investigador(a)


Linhas de interesse

Novas vias microbianas

Biossíntese de polissacarídeos micobacterianos

Biologia de micobactérias não tuberculosas

Estudos de microbioma em doenças crónicas

Visão Geral

Apesar dos avanços monumentais da ciência nas últimas décadas, as doenças infecciosas continuam a ser uma das principais causas de morte no mundo. Essa situação é exacerbada pelo aumento galopante das resistências a fármacos antimicrobianos que crescem em sinergia com as fragilidades de populações idosas e com a prevalência crescente de doenças crónicas decorrentes de fatores ambientais e estilo de vida. Consequentemente, a investigação de doenças infecciosas e outras requer agora uma abordagem integrada que inclua o papel do microbioma intestinal humano.

As micobactérias matam milhões de seres humanos há tempo demais e melhores tratamentos são mais urgentes do que nunca (OMS, 2017). Embora os genomas de Mycobacterium tuberculosis e de micobactérias não tuberculosas (MNT) estejam disponíveis há vários anos, as funções de muitos genes permanecem por desvendar, o que atrasa o caminho para novas terapias. Considerando que somos diariamente expostos a MNT e que esta ameaça tem sido negligenciada, pretendemos investigar a biossíntese de polissacarídeos micobacterianos vitais para identificação de novos alvos para terapias inovadoras e também explorar a biologia da adaptação das MNT a ambientes artificiais, em especial a redes de distribuição de água municipal onde são ubíquas mas não são monitorizadas.

O nosso grupo está também focado em decifrar assinaturas microbianas no intestino disbiótico em doenças neurodegenerativas e outras doenças crónicas, com vista ao desenvolvimento de abordagens preventivas ou bacterioterapêuticas que combinem dados de NGS e as colecções de culturas únicas destes ambientes que implementámos recentemente no CNC. Nesse contexto, estamos interessados em identificar vias microbianas para a biossíntese de metabolitos neuroactivos e como eles modulam a microbiota e a susceptibilidade a doença.

Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria

Esteves AR; Alarico S, 2021. Gut. 1 - 17. 2021. http://dx.doi.org/10.1136/gutjnl-2021-326023 . 10.1136/gutjnl-2021-326023 . published Gut

The neuromicrobiology of Parkinson's disease: A unifying theory

Muñoz-Pinto MF, 2021. Ageing Research Reviews. 70. 2021. http://dx.doi.org/10.1016/j.arr.2021.101396 . 10.1016/j.arr.2021.101396 . published Ageing Research Reviews

Improved diabetic wound healing by bovine lactoferricin is associated with relevant changes in the skin immune response and microbiota

Mouritzen MV, 2021. Molecular Therapy - Methods & Clinical Development. 726 - 739. 20. 2021. https://doi.org/10.1016/j.omtm.2021.02.008 . 10.1016/j.omtm.2021.02.008 . published Molecular Therapy - Methods & Clinical Development

The Mitochondrial Ribosome: A World of Opportunities for Mitochondrial Dysfunction Toward Parkinson's Disease

Gonçalves AM, 2021. Antioxidants & Redox Signaling. 694 - 711. 8. 34. 2021. https://www.liebertpub.com/doi/10.1089/ars.2019.7997 . 10.1089/ars.2019.7997 . published Antioxidants & Redox Signaling

Editorial: Interplay Between Nutrition, the Intestinal Microbiota and the Immune System

Oriá RB, 2020. Frontiers in Immunology. 11. 2020. http://dx.doi.org/10.3389/fimmu.2020.01758 . 10.3389/fimmu.2020.01758 . published Frontiers in Immunology

Stabilization of blood for long-term storage can affect antibody-based recognition of cell surface markers

Silva MB; Färnert A, 2020. Journal of Immunological Methods. 481. 2020. http://dx.doi.org/10.1016/j.jim.2020.112792 . 10.1016/j.jim.2020.112792 . published Journal of Immunological Methods

Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation and Alzheimer's disease features in cortical neurons

Silva DF, 2020. Journal of Neuroinflammation. 332. 17. 2020. http://dx.doi.org/10.1186/s12974-020-02004-y . 10.1186/s12974-020-02004-y . published Journal of Neuroinflammation

A genuine mycobacterial thermophile: Mycobacterium hassiacum growth, survival and GpgS stability at near-pasteurization temperatures

Alarico S, 2020. Microbiology. 474 - 483. 5. 166. 2020. http://dx.doi.org/10.1099/mic.0.000898 . 10.1099/mic.0.000898 . published Microbiology

Microbial BMAA and the Pathway for Parkinson's Disease Neurodegeneration

Nunes-Costa D, 2020. Frontiers in Aging Neuroscience. 12. 2020. https://doi.org/10.3389/fnagi.2020.00026 . 10.3389/fnagi.2020.00026 . published Frontiers in Aging Neuroscience

The structural characterization of a glucosylglycerate hydrolase provides insights into the molecular mechanism of mycobacterial recovery from nitrogen starvation

Cereija TB, 2019. IUCrJ. 572 - 585. 4. 6. 2019. https://doi.org/10.1107/S2052252519005372 . 10.1107/S2052252519005372 . published IUCrJ

High-Quality Draft Genome Sequences of Rare Nontuberculous Mycobacteria Isolated from Surfaces of a Hospital

Tiago I, 2019. Microbiology Resource Announcements. 21. 8. 2019. https://doi.org/10.1128/MRA.00496-19 . 10.1128/MRA.00496-19 . published Microbiology Resource Announcements

Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides

Ripoll-Rozada J; Pereira PJB; Empadinhas N, 2019. Proceedings of the National Academy of Sciences. 201813450 - 201813450. 2019. https://www.pnas.org/content/116/3/835.long . 10.1073/pnas.1813450116 . published Proceedings of the National Academy of Sciences

Studies of antimicrobial resistance in rare mycobacteria from a nosocomial environment

Pereira SG, 2019. BMC Microbiology. 1. 19. 2019. http://dx.doi.org/10.1186/s12866-019-1428-4 . 10.1186/s12866-019-1428-4 . published BMC Microbiology

Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity

Manso JA, 2019. mBio. 2019. https://doi.org/10.1128/mBio.00239-19 . 10.1128/mBio.00239-19 . published mBio

The Microbiome-Mitochondria Dance in Prodromal Parkinson’s Disease

Cardoso SM, Empadinhas N, 2018. Frontiers in Physiology. 9. 2018. https://www.frontiersin.org/articles/10.3389/fphys.2018.00471/full . 10.3389/fphys.2018.00471 . published Frontiers in Physiology

Production, crystallization and structure determination of a mycobacterial glucosylglycerate hydrolase

Cereija TB, 2017. Acta Crystallographica Section F Structural Biology Communications. 536 - 540. 9. 73. 2017. https://doi.org/10.1107%2Fs2053230x17012419 . 10.1107/S2053230X17012419 . published Acta Crystallographica Section F Structural Biology Communications

Hospital microbial surface colonization revealed during monitoring of Klebsiella spp., Pseudomonas aeruginosa, and non-tuberculous mycobacteria

Farias PG, 2017. Antonie van Leeuwenhoek. 863 - 876. 7. 110. 2017. http://dx.doi.org/10.1007/s10482-017-0857-z . 10.1007/s10482-017-0857-z . published Antonie van Leeuwenhoek

Microbiota of Chronic Diabetic Wounds: Ecology, Impact, and Potential for Innovative Treatment Strategies

Pereira SG, 2017. Frontiers in Microbiology. 8. 2017. https://doi.org/10.3389%2Ffmicb.2017.01791 . 10.3389/fmicb.2017.01791 . published Frontiers in Microbiology

Glucosylglycerate metabolism, bioversatility and mycobacterial survival

Nunes-Costa D, 2016. Glycobiology. 213 - 227. 27. 2016. http://dx.doi.org/10.1093/glycob/cww132 . 10.1093/glycob/cww132 . published Glycobiology

The looming tide of nontuberculous mycobacterial infections in Portugal and Brazil

Nunes-Costa D, 2016. Tuberculosis. 107 - 119. 96. 2016. http://dx.doi.org/10.1016/j.tube.2015.09.006 . 10.1016/j.tube.2015.09.006 . published Tuberculosis

Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides

Maranha A; Clarke AJ, Empadinhas N, 2015. Scientific Reports. 1. 5. 2015. http://dx.doi.org/10.1038/srep13610 . 10.1038/srep13610 . published Scientific Reports

Structure of Mycobacterium thermoresistibile GlgE defines novel conformational states that contribute to the catalytic mechanism

Mendes V, 2015. Scientific Reports. 1. 5. 2015. http://dx.doi.org/10.1038/srep17144 . 10.1038/srep17144 . published Scientific Reports

Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway

Fraga JS, 2015. Scientific Reports. 5. 2015. https://doi.org/10.1038/srep08026 . 10.1038/srep08026 . published Scientific Reports

Autophagy in the fight against tuberculosis

Bento CF, 2014. DNA and Cell Biology. 228 - 242. 4. 34. 2014. https://doi.org/10.1089/dna.2014.2745 . 10.1089/dna.2014.2745 . published DNA and Cell Biology

Mycobacterium hassiacum recovers from nitrogen starvation with up-regulation of a novel glucosylglycerate hydrolase and depletion of the accumulated glucosylglycerate

Alarico S, 2014. Scientific Reports. 1. 4. 2014. http://dx.doi.org/10.1038/srep06766 . 10.1038/srep06766 . published Scientific Reports

The molecular biology of mycobacterial trehalose in the quest for advanced tuberculosis therapies

Nobre A, 2014. Microbiology (United Kingdom). 1547 - 1570. PART 8. 160. 2014. https://doi.org/10.1099/mic.0.075895-0 . 10.1099/mic.0.075895-0 . published Microbiology (United Kingdom)

The plant Selaginella moellendorffii possesses enzymes for synthesis and hydrolysis of the compatible solutes mannosylglycerate and glucosylglycerate

Nobre A, 2013. Planta. 891 - 901. 3. 237. 2013. https://doi.org/10.1007/s00425-012-1808-6 . 10.1007/s00425-012-1808-6 . published Planta

A new bacterial hydrolase specific for the compatible solutes alpha-D-mannopyranosyl-(1,2)-D-glycerate and alpha-D-glucopyranosyl-(1,2)-D-glycerate

Alarico S, 2013. Enzyme and Microbial Technology. 77 - 83. 2. 52. 2013. http://dx.doi.org/10.1016/j.enzmictec.2012.10.008 . 10.1016/j.enzmictec.2012.10.008 . published Enzyme and Microbial Technology

Genome sequence of Mycobacterium hassiacum DSM 44199, a rare source of heat-stable mycobacterial proteins

Tiago I, 2012. Journal of Bacteriology. 7010 - 7011. 24. 194. 2012. DOI: https://doi.org/10.1128/JB.01880-12 . 10.1128/JB.01880-12 . published Journal of Bacteriology

Biosynthesis of mycobacterial methylglucose lipopolysaccharides

Mendes V, 2012. Natural Product Reports. 834 - 844. 8. 29. 2012. https://doi.org/10.1039/C2NP20014G . 10.1039/c2np20014g . published Natural Product Reports

Functional and structural characterization of a novel mannosyl-3-phosphoglycerate synthase from Rubrobacter xylanophilus reveals its dual substrate specificity

Empadinhas N, 2011. Molecular Microbiology. 76 - 93. 1. 79. 2011. https://doi.org/10.1111/j.1365-2958.2010.07432.x . 10.1111/j.1365-2958.2010.07432.x . published Molecular Microbiology

Mycobacterium tuberculosis Rv2419c, the missing glucosyl-3-phosphoglycerate phosphatase for the second step in methylglucose lipopolysaccharide biosynthesis

Mendes V, 2011. Scientific Reports. 1. 1. 2011. http://dx.doi.org/10.1038/srep00177 . 10.1038/srep00177 . published Scientific Reports

Diversity, biological roles and biosynthetic pathways for sugar-glycerate containing compatible solutes in bacteria and archaea

Empadinhas N, da Costa MS, 2011. Environmental Microbiology. 2056 - 2077. 8. 13. 2011. https://doi.org/10.1111/j.1462-2920.2010.02390.x . 10.1111/j.1462-2920.2010.02390.x . published Environmental Microbiology

Two alternative pathways for the synthesis of the rare compatible solute mannosylglucosylglycerate in Petrotoga mobilis

Fernandes C, 2010. Journal of Bacteriology. 1624 - 1633. 6. 192. 2010. https://doi.org/10.1128/JB.01424-09 . 10.1128/JB.01424-09 . published Journal of Bacteriology

Biochemical characterization of the maltokinase from Mycobacterium bovis BCG

Mendes V, 2010. BMC Biochemistry. 2010. https://doi.org/10.1186/1471-2091-11-21 . 10.1186/1471-2091-11-21 . published BMC Biochemistry

Identification of the mycobacterial glucosyl-3-phosphoglycerate synthase

Empadinhas N, 2008. FEMS Microbiology Letters. 195 - 202. 2. 280. 2008. https://doi.org/10.1111/j.1574-6968.2007.01064.x . 10.1111/j.1574-6968.2007.01064.x . published FEMS Microbiology Letters

Crystallization and preliminary crystallographic analysis of mannosyl-3-phosphoglycerate synthase from Rubrobacter xylanophilus

Sá-Moura B, 2008. Acta Crystallographica Section F: Structural Biology and Crystallization Communications. 760 - 763. 8. 64. 2008. https://doi.org/10.1107/S1744309108021490 . 10.1107/S1744309108021490 . published Acta Crystallographica Section F: Structural Biology and Crystallization Communications

A Unique Combination of Genetic Systems for the Synthesis of Trehalose in Rubrobacter xylanophilus: Properties of a Rare Actinobacterial TreT

Nobre A, 2008. Journal of Bacteriology. 7939 - 7946. 24. 190. 2008. http://dx.doi.org/10.1128/jb.01055-08 . 10.1128/jb.01055-08 . published Journal of Bacteriology

Osmoadaptation mechanisms in prokaryotes: Distribution of compatible solutes

Empadinhas N, da Costa MS, 2008. International Microbiology. 151 - 161. 3. 11. 2008. https://europepmc.org/article/med/18843593 . 10.2436/20.1501.01.55 . published International Microbiology

Mycobacterium tuberculosis glucosyl-3-phosphoglycerate synthase: Structure of a key enzyme in methylglucose lipopolysaccharide biosynthesis

Pereira PJB, 2008. PLoS ONE. 11. 3. 2008. https://doi.org/10.1371/journal.pone.0003748 . 10.1371/journal.pone.0003748 . published PLoS ONE

Molecular and physiological role of the trehalose-hydrolyzing a-glucosidase from Thermus thermophilus HB27

Alarico S, 2008. Journal of Bacteriology. 2298 - 2305. 7. 190. 2008. http://www.scopus.com/inward/record.url?eid=2-s2.0-41549086172&partnerID=MN8TOARS . 10.1128/JB.01794-07 . published Journal of Bacteriology

To be or not to be a compatible solute: Bioversatility of mannosylglycerate and glucosylglycerate

Empadinhas N, da Costa MS, 2008. Systematic and Applied Microbiology. 159 - 168. 3. 31. 2008. https://doi.org/10.1016/j.syapm.2008.05.002 . 10.1016/j.syapm.2008.05.002 . published Systematic and Applied Microbiology

Bifunctional CTP:inositol-1-phosphate cytidylyltransferase/CDP-inositol: Inositol-1-phosphate transferase, the key enzyme for di-myo-inositol-phosphate synthesis in several (hyper)thermophiles

Rodrigues MV, 2007. Journal of Bacteriology. 5405 - 5412. 15. 189. 2007. http://www.scopus.com/inward/record.url?eid=2-s2.0-34547629796&partnerID=MN8TOARS . 10.1128/JB.00465-07 . published Journal of Bacteriology

Mannosylglycerate is essential for osmotic adjustment in Thermus thermophilus strains HB27 and RQ-1

Alarico S, 2007. Extremophiles. 833 - 840. 6. 11. 2007. http://www.scopus.com/inward/record.url?eid=2-s2.0-35748948644&partnerID=MN8TOARS . 10.1007/s00792-007-0106-x . published Extremophiles

Glucosylglycerate biosynthesis in the deepest lineage of the Bacteria: Characterization of the thermophilic proteins GpgS and GpgP from Persephonella marina

Costa J, 2007. Journal of Bacteriology. 1648 - 1654. 5. 189. 2007. http://www.scopus.com/inward/record.url?eid=2-s2.0-33947366922&partnerID=MN8TOARS . 10.1128/JB.00841-06 . published Journal of Bacteriology

Single-step pathway for synthesis of glucosylglycerate in Persephonella marina

Fernandes C, 2007. Journal of Bacteriology. 4014 - 4019. 11. 189. 2007. http://www.scopus.com/inward/record.url?eid=2-s2.0-34249786874&partnerID=MN8TOARS . 10.1128/JB.00075-07 . published Journal of Bacteriology

Organic solutes in Rubrobacter xylanophilus: The first example of di-myo-inositol-phosphate in a thermophile

Empadinhas N, 2007. Extremophiles. 667 - 673. 5. 11. 2007. http://www.scopus.com/inward/record.url?eid=2-s2.0-34548303944&partnerID=MN8TOARS . 10.1007/s00792-007-0084-z . published Extremophiles

Diversity and biosynthesis of compatible solutes in hyper/thermophiles

Empadinhas N, da Costa MS, 2006. International Microbiology. 199 - 206. 3. 9. 2006. http://www.scopus.com/inward/record.url?eid=2-s2.0-33750584278&partnerID=MN8TOARS . published International Microbiology

Characterization of the biosynthetic pathway of glucosylglycerate in the archaeon Methanococcoides burtonii

Costa J, 2006. Journal of Bacteriology. 1022 - 1030. 3. 188. 2006. http://www.scopus.com/inward/record.url?eid=2-s2.0-31344453995&partnerID=MN8TOARS . 10.1128/JB.188.3.1022-1030.2006 . published Journal of Bacteriology

Distribution of genes for synthesis of trehalose and mannosylglycerate in Thermus spp. and direct correlation of these genes with halotolerance

Alarico S, 2005. Applied and Environmental Microbiology. 2460 - 2466. 5. 71. 2005. http://www.scopus.com/inward/record.url?eid=2-s2.0-18444382346&partnerID=MN8TOARS . 10.1128/AEM.71.5.2460-2466.2005 . published Applied and Environmental Microbiology

Meiothermus timidus sp. nov., a new slightly thermophilic yellow-pigmented species

Pires AL, 2005. FEMS Microbiology Letters. 39 - 45. 1. 245. 2005. http://www.scopus.com/inward/record.url?eid=2-s2.0-15744405109&partnerID=MN8TOARS . 10.1016/j.femsle.2005.02.011 . published FEMS Microbiology Letters

Specialized Roles of the Two Pathways for the Synthesis of Mannosylglycerate in Osmoadaptation and Thermoadaptation of Rhodothermus marinus

Borges N, 2004. Journal of Biological Chemistry. 9892 - 9898. 11. 279. 2004. http://www.scopus.com/inward/record.url?eid=2-s2.0-1642279326&partnerID=MN8TOARS . 10.1074/jbc.M312186200 . published Journal of Biological Chemistry

A gene from the mesophilic bacterium Dehalococcoides ethenogenes encodes a novel mannosylglycerate synthase

Empadinhas N, 2004. Journal of Bacteriology. 4075 - 4084. 13. 186. 2004. http://www.scopus.com/inward/record.url?eid=2-s2.0-3042523198&partnerID=MN8TOARS . 10.1128/JB.186.13.4075-4084.2004 . published Journal of Bacteriology

The Bacterium Thermus thermophilus , Like Hyperthermophilic Archaea, Uses a Two-Step Pathway for the Synthesis of Mannosylglycerate

Empadinhas N, 2003. Applied and Environmental Microbiology. 3272 - 3279. 6. 69. 2003. http://dx.doi.org/10.1128/aem.69.6.3272-3279.2003 . 10.1128/aem.69.6.3272-3279.2003 . published Applied and Environmental Microbiology

Gamma-Proteobacteria Aquicella lusitana gen. nov., sp. nov., and Aquicella siphonis sp. nov. Infect Protozoa and Require Activated Charcoal for Growth in Laboratory Media

Santos P, 2003. Applied and Environmental Microbiology. 6533 - 6540. 11. 69. 2003. http://www.scopus.com/inward/record.url?eid=2-s2.0-0242573382&partnerID=MN8TOARS . 10.1128/AEM.69.11.6533-6540.2003 . published Applied and Environmental Microbiology

Rubritepida flocculans gen. nov., sp. nov., a New Slightly Thermophilic Member of the a-1 Subclass of the Proteobacteria

Alarico S, 2002. Systematic and Applied Microbiology. 198 - 206. 2. 25. 2002. http://dx.doi.org/10.1078/0723-2020-00116 . 10.1078/0723-2020-00116 . published Systematic and Applied Microbiology

Albidovulum inexpectatum gen. nov., sp. nov., a nonphotosynthetic and slightly thermophilic bacterium from a marine hot spring that is very closely related to members of the photosynthetic genus Rhodovulum

Albuquerque L, 2002. Applied and Environmental Microbiology. 4266 - 4273. 9. 68. 2002. http://www.scopus.com/inward/record.url?eid=2-s2.0-0036729238&partnerID=MN8TOARS . 10.1128/AEM.68.9.4266-4273.2002 . published Applied and Environmental Microbiology

Pathway for the synthesis of mannosylglycerate in the hyperthermophilic archaeon Pyrococcus horikoshii: Biochemical and genetic characterization of key enzymes

Empadinhas N, 2001. Journal of Biological Chemistry. 43580 - 43588. 47. 276. 2001. http://www.scopus.com/inward/record.url?eid=2-s2.0-0035941355&partnerID=MN8TOARS . 10.1074/jbc.M108054200 . published Journal of Biological Chemistry

Biosynthesis of mannosylglycerate in the thermophilic bacterium Rhodothermus marinus. Biochemical and genetic characterization of a mannosylglycerate synthase

Martins LO, 1999. Journal of Biological Chemistry. 35407 - 35414. 50. 274. 1999. http://www.scopus.com/inward/record.url?eid=2-s2.0-0033544948&partnerID=MN8TOARS . 10.1074/jbc.274.50.35407 . published Journal of Biological Chemistry

Prémios

2017

Prémio Thomé-Villar, Sociedade Portuguesa de Pneumologia/Boehringer Ingelheim

2016

Prémio Santa Casa Neurociências Mantero Belard, Santa Casa da Misericórdia de Lisboa

2012

19th Exploratory Research Grant, Mizutani Foundation for Glycoscience, Japan

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