Microorganisms play a central role in our existence. They help to digest our food, and they are used to preserve food. Yet, they can spoil food and can poison us. They cause life-threatening infections but also produce the antibiotics that save us. They play key roles in nature as they help the global recycling of nutrients and energy. Considering their importance, it is surprising how little we know about their workings.
The Microbiology theme of SILS studies the molecular mechanisms involved in these processes, works on techniques to prevent microbial pathogens, and develops novel ways to employ microbes for biotechnological applications.
The Amsterdam Microbiome Initiative (AMI) is an Amsterdam wide initiative to bundle the expertise available in our area at the UvA, VU, Amsterdam UMC and ACTA. Its members meet at the Amsterdam Microbiology SeminArs (AMSA) and have as aim to study microbial consortia in biotechnological, biomedical and environmental settings using multidisciplinary approaches.
Spore forming organisms are spoilage organisms of prime-importance to the food industry due to their highly stress resistant endospores. These spores are also prominent in our gastro-intestinal tract. Their occurrence necessitates the application of harsh food preservation. The mechanistic basis of their extreme high thermal resistance (> 121˚C), as well as the molecular mechanisms of spore outgrowth are still characterized by many open questions.
With the help of molecular biology, advanced fluorescence microscopy and proteomics, we investigate ‘Germinosome’ complex required for spore germination, using the model system Bacillus subtilis and the pathogens Bacillus cereus and Peptoclostridium difficile. Studies are currently extended with the AMC to the functional analysis of the gut microbiome.
It is estimated that 50% to 80% of all antibiotics used are applied in agriculture. Veterinary and environmental microbes are often exposed to sublethal levels of antibiotics. Exposure to sublethal drug concentrations induces resistance, transfer of antimicrobial resistant (AMR) genes, and selection for already existing resistance. Novel approaches such as combination or alternating therapy are promising, but need to be investigated in detail before they can be implemented in daily practice.
Of particular interest are environmental conditions encountered by the fungi (yeasts and filamentous fungi) in food, in industrial production conditions, and in disease. As many of these conditions also affect central intracellular or metabolic parameters such as energy or intracellular pH, these have had our particular attention.
For a long time, it was thought that it was crucial for cells to maintain a constant, neutral pH. We have found that pH in yeast is far from constant.
How internal changes in pH control cellular growth, transcription, and signal transduction is being investigated using molecular genetic and microscopic techniques.
As a crucial part of the developing Biobased Economy, the chemical industry is looking for alternative, sustainable, production processes for all/most of their bulk and fine chemicals, fuels, pharmaceuticals and food ingredients. Microbial fermentation is one of the key technologies for biobased production of these chemicals. The work, focusses on three areas of fermentation: (i) Anaerobic fermentation, involving Clostridium, for production of various alcohols from (biological) waste streams and C1-gasses (syngas), (ii) Lipid-producing and lipid-converting microorganisms such as Cryptococcus and Pseudomonas that can produce and convert various medium- and long-chain fatty acids, and (iii) Lactic acid bacteria as producer of natural flavors, of preservatives and for nutritional enrichment of food products. The described work is an important part of the Amsterdam Green Campus
Cell division is a vital process, and yet, we still do not know exactly how bacterial cells divide. We use the well-known bacterial model system Bacillus subtilis to study the dynamic interaction between cell division proteins using molecular biological and fluorescence microscopy and techniques. This latter technique is also very useful to study the mode of action of novel antimicrobial compounds, which is called bacterial cytological profiling. We this and other tools to identify and characterize new antimicrobial compounds.
B. subtilis is used in the bioindustry to produce enzymes and vitamins. The bacterium is also used as a probiotic in animal feed, and in fact it is eaten by humans in the form of Natto. In collaboration with industrial partners we help to further optimize B. subtilis for applied purposes.
The morphology of rod-shaped bacteria is achieved through two very dynamic synthetic complexes: the elongasome and the divisome. The elongasomes are recruited by the actin-like cytoskeleton MreB protein and move in an helical path to insert new peptidoglycan subunits along the cell envelope. The divisome is responsible for division. Cell division is directed by the FtsZ ring (a tubulin homolog). How the elongasome and divisome work is still surrounded by questions that we investigate in vivo using immunofluorescence and fluorescence microscopy techniques (FRET, FLIM, FRAP, immunolocalization) and in vitro using biochemical and biophysical techniques.
Elongasome and divisome proteins are essential and provide ideal antibiotic targets. We develop fluorescence-based assays to find and study new antimicrobial compounds to target these proteins.
We aim to integrate knowledge on the biochemical and biophysical properties of signal transduction- and metabolic networks that regulate and underlie fermentation, respiration and oxygenic photosynthesis. Ultimately, we want to understand how the environment, through evolution and natural selection, shapes microbes to be equipped with the capacity to deal with the fluctuations they encounter. For our studies, we focus on the industrially relevant lactic acid bacterium Lactococcus lactis and the model organism for studies in oxygenic photosynthesis Synechocystis PCC6803. Both organisms are highly relevant for the transition of our society towards a sustainable bio-based economy.