SPRINGBOARD is funded by the European Union Research and Innovation programme Horizon 2020 under the Twinning call Spreading excellence and widening participation (Grant no. 951883, 2020-2023). The main goal of the project is to strengthen the research potential of the Latvian Institute for Organic Synthesis (LIOS) in the field of advanced discovery and design of novel antibacterial drugs through establishing a sustainable and long-term collaboration with leading counterparts – University of Antwerp, University of Copenhagen, University of Florence and University of Helsinki. The coordinator of this project is Professor Raivis Žalubovskis from LIOS.
The rapid emergence and spread of antimicrobial resistance is leading us to dramatic post-antibiotic scenarios where life-threatening infections are reality for increased numbers of patients. Thereby, there is an urgent need worldwide for action plans incorporating higher levels of public and private investment to develop new effective antibiotics. Infections caused by Gram-negative bacteria occupy the top of WHO’s list describing pathogens that are most critical for development of new antibacterials due to their prominent prevalence in hospital-acquired infections and multi-drug resistance. Our project aims to develop next generation antibiotics against Gram-negative bacteria through a holistic approach entailing seamless co-operation of multidisciplinary research teams of experts in medicinal chemistry, microbiology, molecular dynamics, in silico modelling and nanomedicine. This projects is funded by the Academy of Finland Grant no. 321551 (2019-2023).
Overexpression of efflux pumps is a major factor for drug resistance in Gram-negative bacteria. In E. coli, the AcrAB-TolC efflux pump complex transports antibiotics from the periplasm or cytoplasm into the external medium. As TolC deletion has been shown to result in increased susceptibilities of E. coli to several antibiotics, it may represent an attractive drug target. Building on our previous results, we focus on development of novel TolC blockers within an interdisciplinary consortium, coordinated by Fraunhofer IME. The project workflow includes compound modifications by medicinal chemistry, assessment of TolC binding and blockage using SPR and electrophysiology, various antimicrobial studies and ADMETox profiling. Novel small molecules blocking TolC will be identified and optimised using the same experimental platform, starting with virtual screening for identification of novel compounds targeting TolC. Ultimately, this approach will allow to assess TolC target validity for adjuvants in antimicrobial therapies and result in potent TolC blockers that may be further developed into drugs restoring E. coli susceptibility to antibiotics. This project is funded by the 6th transnational call for the JPIAMR within the ERA-NET JPI-EC-AMR (Academy of Finland Grant no. 326261, 2019-2022). Further details
Novel compounds with potential antimicrobial properties are continuously discovered, for example from natural products, but in many cases found activities are not being characterised beyond the initial discovery phase. In this project, our aim was to develop predictive and efficient tools for the antibacterial screening process and follow-up studies. This project was funded by the Academy of Finland (2014-2019, Academy of Finland Fellowship).
The INTEGRATE training framework was built on an innovative research project aimed at targeting important but non-essential gene products as an effective means of reducing bacterial fitness, thereby facilitating clearance of the pathogen by the host immune system. To achieve this, the individual work programmes were designed to seamlessly inter-mesh contributions from the fields of in silico design, organic synthesis, molecular biology and biochemistry, and the very latest in vitro and in vivo screening technologies. This project was funded by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642620 (2014-2018).
In this project, we aimed to fully explore the antibacterial potential of natural product –based synthetic compounds that were found to display highly promising activity against Gram-positive bacteria. The project was funded by the Academy of Finland (2016-2018, Key project).