REBEL
Repotentiating Beat lactam antibiotics (REBEL)
Resistance to beta-lactam antibiotics is a major problem in health care. Often this problem is caused by bacteria that produce beta-lactamase enzymes, which degrade this group of antibiotics. This can be prevented by administering the antibiotic together with a substance which inhibits the enzyme from the bacterium. In this way existing beta-lactam antibiotics can be made usable again. Mariël Pikkemaat is coordinating a consortium of Canadian, Swedish and Dutch researchers working in a JPI Anti-Microbial Resistance project to find new beta-lactamase inhibitors.
The number of inhibiting compounds that have actually made it to clinical application is extremely limited. The aim of the project REpotentiating BEta Lactam antibiotics (REBEL) is to discover and characterise new molecules of botanical origin that selectively inhibit beta-lactamases, yielding new lead compounds. For this purpose a wide range of plant extracts will be screened for their potency. From extracts that show inhibition, the bioactive compounds will be isolated and identified. Promising molecules will be further examined to determine how they inhibit and whether they have a chance for clinical application ultimately to combat resistant bacteria.
"Very inspiring how research collaboration can be achieved"
Mariël Pikkemaat was not yet familiar with JPI before she initiated the REBEL project. Through a project application in the national program priority medicines of ZonMw however, she was invited to the national consultation for the Strategic Research Agenda of JPIAMR. There she was told that soon a first call would come, and that in addition to EU members also Canada would participate substantially. Mariël Pikkemaat was immediately triggered by the first call of JPI AMR. "It is a very urgent issue and this call was really focused on finding solutions."
"The project fits well with techniques that we use at RIKILT for the antibiotic residue screening combined with the advanced facilities we have in analytical chemistry field and our interest in herbs as an alternative to antibiotics."
Nevertheless, for RIKILT this particular topic is not a core business. Even in the Netherlands not all required expertise is available. The Partnering Tool JPI AMR was helpful to find the research partners with the desired expertise and sufficient budget available per country. “Very inspiring how such research collaboration can be achieved”.
In the project, started in February 2015, the tasks are allocated to expertise. RIKILT performs the screening of the plant extracts. The screening strategy involves miniaturized growth inhibition assays based on a range of modified E. coli bacteria expressing different (types of) beta-lactamases. Extracts showing beta-lactamase inhibitory activity will be profiled and a selection of the most promising extracts will be subjected to further isolation, identification and structural confirmation of the bioactive compound.
After verification of the inhibitory capacity of the new compounds, design and synthesis of analogues will be initiated by Umeå University, Sweden. The University of British Columbia, Canada will carry out a full characterization of the newly identified inhibitors and analogues using biochemical and crystallographic studies will be carried out. Ultimately this project should yield the identification of new lead compounds for the development of clinical β-lactamase inhibitors.
Researchers in the spotlight with projects funded through jointly programmed calls
One of the aims of joint programming is aligning research & research funding and this usually results in a joint call to which proposals can be submitted. In a series of interviews, researchers from Wageningen University and Research present their granted projects from such joint calls.