Professor Thomas Bjarnsholt
Costerton Biofilm Centre, University of Copenhagen
Head of Molecular Diagnostic Laboratory, Copenhagen University Hospital
“Bacteria growing in the biofilm state represent a challenging burden for the health system and by exploring the nature and antibiotic response of bacteria in this state we can increase the understanding and treatment of infections caused by bacteria in biofilm.
Our recent research show that the metabolism of bacteria determines their antibiotic tolerance. So far, the distinguishing between planktonic single bacteria and biofilms has only been possible by microscopy. We would very much like more quantitative data on the different bacterial populations.
This we hope to accomplish by using the calScreener to study the metabolism of planktonic bacteria and bacteria in in vitro and ex vivo biofilm, to investigate the optimal treatment of in vitro and in vivo bacterial biofilm. The calScreener will be used to investigate how the metabolic activity levels of bacteria in biofilms are correlated with efficiency of antibiotic treatment.
Our initial results are very promising, and I foresee the calScreener™ to be an extremely important tool, for elucidating how to treat and prevent chronic infections in the future.”
Professor Tom Coenye
Laboratory of Pharmaceutical Microbiology, University of Ghent
“In my research group, the Laboratory of Pharmaceutical Microbiology at Ghent University, we are particularly interested in bacterial biofilms involved in different infections, including respiratory tract infections. One of the hallmarks of biofilms is their reduced susceptibility to antibiotics, and in my lab we focus on obtaining novel insights into the mechanisms behind biofilm tolerance.
From ongoing research it has become clear that changes in metabolism observed in biofilm-grown bacteria play an important role, but so far the tools to study bacterial metabolism were lacking. The calScreener™ has made it possible to study metabolism in biofilm aggregates formed under relevant conditions (in a simulated sputum medium) and we have indeed been able to observe marked changes in metabolism over the course of a simulated infection.
In addition, microcalorimetry showed that resistance mutations induced by repeated exposure to antibiotics under these conditions also affect bacterial metabolism, and these insights will pave the way for translational research in which we will try to ‘rewire’ biofilm metabolism to increase susceptibility to antibiotics.
We believe the calScreener™ device will be very useful in future work on metabolism in bacterial biofilms and could become an essential tool in our work.”
Professor Christian Giske
Chief Physician, Clinical Microbiology, Karolinska Hospital
Chairman, European committee on antimicrobial susceptibility testing (EUCAST)
“Antimicrobial resistance is increasing rapidly and can cause infections that are extremely difficult to treat. Sometimes not even a single antimicrobial has remaining activity against these pathogens. The only possible management is customized solutions with rapid and accurate quantitative measurements. Moreover, there is a great need for testing several antimicrobials simultaneously, to predict the effects of combination therapy. Thus far there is no existing commercial solution for this problem which could be feasible to use in clinical laboratories.
The calScreener™ is uniquely positioned to potentially solve these problems and this is what enthused us to start testing Symcel’s technology in our research lab.”
Assistant Professor Willem van Wamel
Head of the Staphylococcus Group, Medical Microbiology Department at Erasmus MC
"Isothermal microcalorimetry allows us to observe in real-time the metabolic status of biofilm associated bacteria and therefore to select the antibiotics that are active against them."
Dr. Jennifer Herrmann
Research Scientist in Professor Rolf Muller's group, Helmholtz Centre for Infection Research
“The design of the calScreener™ is outstanding as it utilizes the change in heat produced by living organisms in real-time without manual intervention. This allows e.g. for the observation of bacterial metabolism in response to antibiotic treatment.
One of our research foci is the investigation of anti-infective properties of small molecules derived from Myxobacteria and other environmental bacteria. Here, the calScreenerTM has shown to be a reliable tool in the determination of key parameters such as minimal inhibitory concentrations and mutation-induced fitness cost and its correlation to specific genotypes. In addition, with the help of the calScreenerTM we can easily distinguish between bacteriostatic and bactericidal mechanisms of our compounds. The initial results of our studies with bacterial pathogens in vitro as well as in vivo using zebrafish larvae as infected host look very promising and we are looking forward to see how the calScreenerTM will further contribute to the discovery of new anti-infectives from natural products.”
Dr. Suado Abdillahi
“Colzyx has developed novel antibacterial peptides derived from Collagen VI.
We have extensively characterized the killing activity against both Gram-positive and Gram-negative bacteria in vitro and gained detailed insight in the bactericidal nature of these peptides.
The calScreener™ metabolic rates assay further shows the different impact on bacterial growth both on inhibition properties as well as the potency of bacterial killing in a planktonic growth system using P.aeruginosa as model organism. Calorimetric assessment of growth inhibition is a valuable tool to determine the properties of lead drug candidates and rank the desired properties.”
Dr. Olivier Braissant
Senior Researcher, University of Basel
“The calScreener is an instrument combining high sensitivity and high throughput. This instrument is ideal for most biotechnology purposes involving organisms from bacteria to small nematodes. As a consequence, a few thousand cells are already sufficient to have a clear thermal response. It is particularly well suited for drug susceptibility assays and metabolic studies.
The calScreener perfectly complements other thermal analysis tools such as DSC or ITC in biotech environment and drug discovery. It is also a valuable alternative to other time consuming techniques and assays.”
Dr. Anni-Maria Örmälä-Odegrip
Senior Postdoc and Scientific Study Leader, Clinical Microbiology Department at Karolinska Hospital
“The calScreener is a unique device for monitoring bacterial growth – or inhibition of growth by antimicrobials. The most valuable attribute with the technique is that by monitoring the heat released in the system, it allows you to observe the bacterial metabolism in real-time, as opposed to optical methods, where the bacterial debris or metabolically inactive cells will give a signal – often resulting in a lag in the data.
In antimicrobial susceptibility testing we have been able to significantly cut down the time that it takes to observe if a given antimicrobial inhibits the growth of the bacteria. In bacterial growth measurements for analyzing the bacterial fitness, the unique metabolic patterns of individual species or isolates give us much more resolution on the analysis, and sometimes we have been a bit puzzled by being able to see phenomena that we would not track with other methods. But this is definitely a positive problem!
Our next step is to start routinely using calScreener for the screening process of selecting suitable bacteriophages for phage therapy for multidrug-resistant bacteria. The characteristics of the device are perfect for observing the detailed dynamics between the bacterial hosts and their viral parasites, giving us valuable information on which phages should be selected for further trials in the development process.”