Molecular Microbiology and Microbiome

Nuno Empadinhas

PhD, Group Leader

Infectious diseases remain one leading cause of death worldwide. This pressing situation is further compounded by the immune vulnerabilities associated with the rising rates of chronic diseases and aging populations, and by the inexorable antimicrobial resistance trend worldwide.

Our group is focused on mycobacterial pathogens, “a globally established priority for which innovative new treatments are urgently needed” (WHO 2017). We have deciphered biosynthetic pathways for stress metabolites and mycobacterial polysaccharides considered promising targets for tuberculosis (TB) therapies. Over the years, we have unveiled enzyme activities that were the founding members of 15 new IUBMB families (https://www.enzyme-database.org/query.php?name=Empadinhas).

An integrated approach that incorporates the human microbiome has become mandatory to investigate brain, metabolic and also infectious diseases, a new paradigm that will soon provide new tools to prevent, halt or treat disease. Articulation of this group’s expertise with the biomedical and biotechnological strengths in the Innovative Therapies strand and across the CIBB will drive fruitful scientific and translational outputs. In 6 years this group secured over 800k euro in research funding, including recent grants to investigate diabetic wounds microbiota and the microbiome-gut-brain axis in Parkinson's Disease.

Research in diseases, whether brain, metabolic or infectious, should now also inevitably integrate the human microbiome, in a new paradigm that is deemed to unveil important new tools to prevent, stop or treat them. The articulation of our experience with CIBB's strengths allowed securing multiple grants, shared supervision of PhD students, and high-impact joint publications, in addition to those wit external collaborators.

Group Members

Group Members

Group memberes are: Nuno Empadinhas (PhD, Group Leader), Ana Maranha (PhD), Ana Dias, Daniela Nunes-Costa, Inês Roxo, John D. Marugg (PhD), Sara Gonçalves, Susana Alarico (PhD).

Selected Publications

Esteves AR, Muñoz-Pinto M, Nunes-Costa D, Candeias E, Silva DF, Magalhães JD, Pereira-Santos AR, Ferreira IL, Alarico A, Tiago I, Empadinhas N, Cardoso SM (2021) Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria. Gut. gutjnl-2021-326023. http://dx.doi.org/10.1136/gutjnl-2021-326023.

Muñoz-Pinto M, Empadinhas N, Cardoso SM (2021) The neuromicrobiology of Parkinson’s disease: A unifying theory. Ageing Research Reviews 70:101396. https://doi.org/10.1016/j.arr.2021.101396.

Gonçalves AM, Pereira-Santos AR, Esteves AR, Cardoso SM, Empadinhas N (2021) The mitochondrial ribosome: a world of opportunities for mitochondrial dysfunction toward Parkinson’s Disease. Antioxidants & Redox Signaling 34 8: 694-711. https://doi.org/10.1089/ars.2019.7997.

Mouritzen MV, Petkovic M, Qvist K, Poulsen SS, Alarico S, Leal EC, Dalgaard LT, Empadinhas N, Carvalho E, Jenssen H (2021) Improved diabetic wound healing by bovine lactoferricin is associated with relevant changes in the skin immune response and microbiota. Molecular Therapy-Methods & Clinical Development 20:726-739. https://doi.org/10.1016/j.omtm.2021.02.008.

Nunes-Costa D, Magalhães J, G-Fernandes M, Cardoso SM, Empadinhas N (2020) Microbial BMAA and the pathway for Parkinson’s Disease neurodegeneration. Frontiers in Aging Neuroscience 12:26. https://doi.org/10.3389/fnagi.2020.00026.

Cereija TB, Alarico S, Lourenço EC, Manso JA, Ventura MR, Empadinhas N, Macedo-Ribeiro S, Pereira PJB (2019) The structural characterisation of a glucosylglycerate hydrolase provides insights into the molecular mechanism of mycobacterial recovery from nitrogen starvation. IUCrJ 6(4):572-585. https://doi.org/10.1107/S2052252519005372.

Manso JA, Nunes-Costa D, Macedo-Ribeiro S, Empadinhas N, Pereira PJB (2019) Molecular fingerprints for a novel enzyme family in Actinobacteria with glucosamine kinase activity. mBio 10(3) pii: e00239-19. https://doi.org/10.1128/mBio.00239-19.

Ripoll-Rozada J, Costa M, Manso JA, Maranha A, Miranda V, Sequeira A, Ventura MR, Macedo-Ribeiro S, Pereira PJB, Empadinhas N (2019) Biosynthesis of mycobacterial methylmannose polysaccharide requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides. Proceedings of the National Academy of Sciences of the USA 116(3):835-844. https://doi.org/10.1073/pnas.1813450116.

Maranha A, Moynihan PJ, Miranda V, Correia EL, Nunes-Costa D, Fraga JS, Pereira PJB, Macedo-Ribeiro S, Ventura MR, Clarke AJ, Empadinhas N (2015) Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides. Scientific Reports 5:13610. https://doi.org/10.1038/srep13610.

Mendes V, Maranha A, Alarico S, Empadinhas N (2012) Biosynthesis of mycobacterial methylglucose lipopolysaccharides. Natural Product Reports 29(8):834-44. https://doi.org/10.1039/C2NP20014G.

Selected Projects

Nontuberculous mycobacteria from drinking water: beyond the lung disease epidemic. PTDC/BIA-MIC/0122/2021, FCT-Fundação para a Ciência e a Tecnologia (2022-2025)

Microbiome-miRNAs axis in Parkinson’s disease: involvement of mitochondrial mediated inflammatory response. EXPL/MED-NEU/1515/2021, FCT-Fundação para a Ciência e a Tecnologia (2022-2023)

The Gut-Immune-Brain Axis in Parkinson disease. PTDC/MED-NEU/3644/2020, FCT-Fundação para a Ciência e a Tecnologia (2021-2024)

An intriguing mycobacterial polysaccharide: recycling, replication and beyond. PTDC/BTM-TEC/29221/2017 (POCI-01-0145-FEDER-029221), FCT-Fundação para a Ciência e a Tecnologia/POCI (2018-2021)

The toxinogenic gut microbiome in sporadic Parkinson’s Disease: a quest for “AntiPDbiotics”. Mantero Belard Award, Santa Casa da Misericórdia de Lisboa (MB-40-2016) (2017-2020).

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