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Footprints of a microbial toxin from the gut microbiome to mesencephalic mitoch...

Esteves, A. Raquel; Munoz-Pinto, Mário F; Nunes-Costa, Daniela; Candeias, Emanuel; Silva, Diana F. F.; Magalhães, João Duarte; Santos, A. Raquel Pereira

Objective Idiopathic Parkinson’s disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N- methylamino- L- al...


Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans

Gonçalves, Sara; Nunes-Costa, Daniela; Cardoso, Sandra Morais; Empadinhas, Nuno; Marugg, John David

Serotonin is a phylogenetically ancient compound found in animals, plants, and some bacteria. In eukaryotes, serotonin is synthesized from the aromatic amino acid tryptophan via the key enzymes aromatic amino acid hydroxylase (AAAH) and aromatic amino acid decarboxylase (AAAD). Serotonin is also an intermediate in the melatonin biosynthetic pathway and is involved in several vital functions. In humans, serotoni...


Footprints of a microbial toxin from the gut microbiome to mesencephalic mitoch...

Esteves, A. Raquel; Munoz-Pinto, Mário F.; Nunes-Costa, Daniela; Candeias, Emanuel; Silva, Diana F.; Magalhães, João D.; Pereira-Santos, A. Raquel

Idiopathic Parkinson's disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N-methylamino-L-alanine (BMAA) ...


Microbial BMAA and the Pathway for Parkinson's Disease Neurodegeneration

Nunes-Costa, Daniela; Magalhães, João Duarte; G-Fernandes, Maria; Cardoso, Sandra Morais; Empadinhas, Nuno

The neurotoxin β-N-methylamino-L-alanine (BMAA) is a natural non-proteinogenic diamino acid produced by several species of both prokaryotic (cyanobacteria) and eukaryotic (diatoms and dinoflagellates) microorganisms. BMAA has been shown to biomagnify through the food chain in some ecosystems, accumulating for example in seafood such as shellfish and fish, common dietary sources of BMAA whose ingestion may have ...


Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, a...

Silva, Diana F.; Candeias, Emanuel; Esteves, Ana Raquel Fernandes; Magalhães, João Duarte; Ferreira, I. Luísa; Nunes-Costa, Daniela; Rego, Ana Cristina

Background: After decades of research recognizing it as a complex multifactorial disorder, sporadic Alzheimer’s disease (sAD) still has no known etiology. Adding to the myriad of different pathways involved, bacterial neurotoxins are assuming greater importance in the etiology and/or progression of sAD. β-N-Methylamino-L-alanine (BMAA), a neurotoxin produced by some microorganisms namely cyanobacteria, was prev...


Studies of antimicrobial resistance in rare mycobacteria from a nosocomial envi...

Pereira, Sónia Gonçalves; Alarico, Susana; Tiago, Igor; Reis, Diogo; Nunes-Costa, Daniela; Cardoso, Olga; Maranha, Ana; Empadinhas, Nuno

Background: Nontuberculous mycobacteria (NTM) are ubiquitous in nature and recognized agents of opportunistic infection, which is often aggravated by their intrinsic resistance to antimicrobials, poorly defined therapeutic strategies and by the lack of new drugs. However, evaluation of their prevalence in anthropogenic environments and the associated antimicrobial resistance profiles have been neglected. In thi...


Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosa...

Manso, José A.; Nunes-Costa, Daniela; Macedo-Ribeiro, Sandra; Empadinhas, Nuno; Pereira, Pedro José Barbosa

Actinobacteria have long been the main source of antibiotics, secondary metabolites with tightly controlled biosynthesis by environmental and physiological factors. Phosphorylation of exogenous glucosamine has been suggested as a mechanism for incorporation of this extracellular material into secondary metabolite biosynthesis, but experimental evidence of specific glucosamine kinases in Actinobacteria is lackin...


Octanoylation of early intermediates of mycobacterial methylglucose lipopolysac...

Maranha, Ana; Moynihan, Patrick J.; Miranda, Vanessa; Correia Lourenço, Eva; Nunes-Costa, Daniela; Fraga, Joana; José Barbosa Pereira, Pedro

Mycobacteria synthesize unique intracellular methylglucose lipopolysaccharides (MGLP) proposed to modulate fatty acid metabolism. In addition to the partial esterification of glucose or methylglucose units with short-chain fatty acids, octanoate was invariably detected on the MGLP reducing end. We have identified a novel sugar octanoyltransferase (OctT) that efficiently transfers octanoate to glucosylglycerate ...


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