Lactic Acid Bacteria & In Vivo NMR

The Lactic Acid Bacteria & in vivo NMR group studies regulation of metabolism in bacteria using NMR and molecular techniques. Our research spans mechanisms of virulence in pathogens and metabolic engineering of industrial bacteria.

Research Interests

Our research interests focus on metabolic and transcriptional regulation in Gram-positive bacteria, and in particular the elucidation of mechanisms involved in sugar uptake and degradation. This subject is especially relevant when studying fermentative organisms, in which sugar metabolism is central to physiology. To expand our understanding of the metabolic and regulatory networks, we use as models the human pathogen Streptococcus pneumoniae and the food-grade Lactococcus lactis. We are convinced that these data are useful in (i) the identification of virulence and pathogenic factors (S. pneumoniae) and (ii) in tailoring microbial metabolism for the production of health-promoting compounds (L. lactis), and ultimately will generate fundamental and applied knowledge.

In collaboration with H. Santos (Cell Physiology & NMR, ITQB), we have pursued a line of research initiated about a decade ago, which aims at characterizing central metabolism in the model organism L. lactis. Studying the regulation of the glycolytic pathway, we have succeeded in assigning the function of several unknown genes and identified new metabolic pathways. Our in vivo NMR time-series data are used worldwide for metabolic modelling and allows us and others to direct metabolic engineering towards the production of health-promoting compounds.

The knowledge of in vivo physiology and metabolism of S. pneumoniae is limited, even though pneumococcal pathogenesis also relies on efficient acquisition and assimilation of nutrients. Being a strictly fermentative organism, the ability to take up and metabolize sugars is of chief importance. In the human body S. pneumoniae encounters great variation in sugar composition and availability. Therefore, mechanisms involved in carbon catabolite control are of utmost importance for fitness, survival and virulence in the host. Metabolic pathways and mechanisms involved remain, however, largely elusive. We are addressing questions such as which sugars and pathways are used during colonization, and whether the involved players are essential for persistence. We want to understand how pneumococcus copes with changes in sugar nature and availability and how these mechanisms relate to virulence and pathogenesis. Presently we pursue these goals using molecular biology tools and global approaches such as in vivo NMR for metabolite profiling and proteome analysis. In addition, we use transcriptomics and animal models through international collaborations.

Group Members

• Paula Gaspar, Pos-doc (Co-supervisor H. Santos) pgaspar@itqb.unl.pt
• Ana Lúcia Carvalho, PhD student (Principal supervisor H. Santos) anac@itqb.unl.pt
• Sandra Carvalho, PhD student smcc@itqb.unl.pt
• Laura Paixão, PhD student lpaixao@itqb.unl.pt
• Mafalda Cavaleiro, graduated student mcavaleiro@itqb.unl.pt
• Ricardo Sequeira, graduated student rsequeira@itqb.unl.pt
• Teresa Ferreira, graduated student (Co-supervisor M. Pinho) tferreira@itqb.unl.pt

Selected Publications

1. H. Yesilkaya, F. Spissu, S. M. Carvalho, V. S. Terra, K. A. Homer, R. Benisty, N. Porat, A. R. Neves & P. W. Andrew. Pyruvate formate lyase is required for pneumococcal fermentative metabolism and virulence. Accepted for publication in Infection and Immunity (2009).
2. R. Castro, A. R. Nevesa, L. L. Fonseca, W. A. Pool, J. Kok, O. P. Kuipers & H. Santos. Characterization of the individual glucose uptake systems of Lactococcus lactis: mannose-PTS, cellobiose-PTS and the novel GlcU permease. Mol. Microbiol. 71, 795–806 (2009) aCorresponding author.
3. E. O. Voit, A. R. Neves & H. Santos. The intricate side of systems biology. Proc. Nat. Acad. Sci. USA. 103, 9452-9457 (2006).
    

Laboratory's Website

For further information visit the laboratory's website 

Bactérias do Ácido Láctico e RMN in vivo (PT)

As bactérias lácticas são um grupo bastante diverso de microrganismos cuja principal característica é a produção de ácido láctico. Algumas espécies são utilizadas na indústria alimentar, enquanto outras são reconhecidos organismos patogénicos que causam doenças como pneumonia e meningite. Posto isto, é compreensível que estas bactérias suscitem um grande interesse científico.

No laboratório estudamos regulação das vias metabólicas no organismo patogénico Streptococcus pneumoniae e no produtor de queijo Lactococcus lactis. O nosso objectivo é compreender os mecanismos celulares envolvidos no transporte e degradação de açucares, nutrientes essenciais para o crescimento destas bactérias. Para tal, usamos ferramentas de biologia molecular e engenharia genética, bem como uma técnica não invasiva que permite monitorizar células intactas, a Ressonância Magnética Nuclear. O conhecimento gerado tem potencial no desenvolvimento de aplicações biotecnológicas e/ou terapias alternativas.

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