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Sarela Garcia-Santamarina

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The Human Microbiota – Xenobiotics Interactions Lab investigates the effects of metals (and other xenobiotics) in the gut microbiota composition and function and its effects on the host by combining systems-based approaches and tailored molecular and biochemical experiments.

Sarela Garcia-Santamarina
Auxiliary Investigator
PhD 2013 in Biomedicine,
University Pompeu Fabra, Spain

Email sarela.santamarina@itqb.unl.pt

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Research Interests

In recent years there has been an increased awareness of the importance of the human microbiome for health and disease. In fact, the genes in our microbiome outnumber our genes in a ratio of 150:1. This results in a human microbiome with a high capacity to influence us in a variety of physiologic, immunologic and metabolic processes. Thus, alterations of the human microbiome have been implicated in gastrointestinal, cardiovascular, psychologic, respiratory, oncologic, hepatic and autoimmune diseases.

Ingested substances, including nutrients or xenobiotics, have the biggest influence in the composition and function of the gut microbiome and in its interaction with the host. Among ingested substances, transition metals are particularly interesting. Metals are essential for life: both the microbiota and the host require homeostatic metal concentrations for proper functioning of about 50% of their proteins. But, when in excess, metals are toxic. Despite the relevance of homeostatic metal concentrations for microbial and human physiology, the effects of trace element concentrations in gut microbiome composition and function (i.e. metabolism), in human nutrition and in host-microbial interactions during commensalism, are not well understood and remain largely unexplored. Importantly, millions of people worldwide have severe, life-threatening deficiencies in metals of biological relevance (Fe, Zn, Cu, …) due to poor nutrition, low metal absorption rates or genetic diseases. In addition, by getting exposed to contaminated sources, millions of people accumulate heavy metals (Pb, Hg, Cd, As, …), with severe consequences for their health.

The Human Microbiota – Xenobiotics Interactions Lab aims to investigate the effects of metals in the gut microbiota composition and function and its effects on the host using high-throughput experimental platforms and innovative technologies to answer the following questions:

  • What is the fitness of gut microbes in the presence of diverse metal concentrations? Do metals affect bacterial communities’ structure? Are bacterial pathobionts or pathogens outcompeting commensals at certain concentrations of metals?
  • How is the gut microbiota metabolism, highly dependent on metalloenzymes, affected by different metal environments?
  • How does the gut microbiota influences metals (or metal-dependent synthesized metabolites) absorption by human cells at different metal concentrations? And vice versa, how host cells absorption of metals affects the gut microbiota composition and function?

The long-term goal is to contribute to a better understanding of microbial physiology and responses to fluctuating micronutrient concentrations, as well as shed light into host-microbial interactions that might have a direct role in host nutrition. In the future, this research will be expanded to pathophysiological situations where the gut microbiota plays an important role to answer questions like how nutritional competition between host cells and microbes impacts disease progression (e.g. inflammatory bowel disease or cancer).

 

Selected Publications

  1. García-Santamarina S., Probst C., Festa R.A., Ding C., Smith A.D., Conklin S.E., Brander S., Kinch L.N., Grishin N.V., Franz K.J., Riggs-Gelasco P., Lo Leggio L., Johansen K.J., Thiele D.J. (2020) A Lytic Polysaccharide Monooxygenase-like protein functions in copper import and fungal meningitis. Nature Chemical Biology 16(3):377-344.
  2. García-Santamarina, S., Festa, R.A., Smith, A.D., Yu, C.H., Probst, C., Ding, C., Homer, C.M., Yin, J., Noonan, J.P., Madhani, H., Perfect, J.R., Thiele, D.J. (2018) Genome-wide analysis of the regulation of Cu metabolism in Cryptococcus neoformans. Molecular Microbiology. 108 - 5, pp. 473 - 494.
  3. García-Santamarina, S., Uzarska, M.A., Lill, R. and Thiele, D.J. (2017) Cryptococcus neoformans iron-sulfur protein biogenesis machinery is a novel layer of protection against Cu stress. mBio 8 - 5, pp. e01742-17.
  4. García-Santamarina, S., and Thiele, D.J. (2015) Copper at the fungal pathogen-host axis.  Journal of Biological Chemistry 290(31):18945-18953.
  5. García-Santamarina, S., Boronat, S., Domènech, A., Ayté, J., Molina, H. and Hidalgo, E. (2014) Monitoring in vivo cysteine oxidation in proteins – global maps of reversibly oxidized thiols using ICAT and LC-MS/MS. Nature Protocols. 9(5):1131-45.

 

Laboratory's Website

For further information visit the laboratory's website (soon available).
 

Interações da microbiota humana com xenobióticos (PT)

A microbiota intestinal tem sido postulada nos últimos anos como um fator de grande relevância para a saúde, com influência numa variedade de processos fisiológicos, imunológicos e metabólicos. Assim, as alterações no microbioma têm sido associadas a doenças gastrointestinais, cardiovasculares, psicológicas, respiratórias, oncológicas, hepáticas e autoimunes.

As substâncias que ingerimos, nutrientes, drogas, etc, influenciam muito a composição e função da microbiota intestinal e sua interação com o hospedeiro. Entre estas substâncias estão os metais de transição, que, apesar de essenciais à vida, tanto para a microbiota como para o hospedeiro, em excesso são tóxicos. Com a nossa pesquisa, pretendemos compreender melhor a fisiologia e as respostas microbianas às variações nos micronutrientes, neste caso os metais de transição, bem como as interações microbiota-hospedeiro, que podem ter um impacto direto na nutrição e na saúde do hospedeiro.

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