Antimicrobial resistance (AMR), particularly among gram-negative bacteria, has escalated to the point where routine treatments for common infections and minor injuries may soon become ineffective—unless coordinated, cross-sector efforts are urgently implemented. The need for new antimicrobial solutions has been widely recognized by global health authorities such as the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC), and the European Medicines Agency (EMA). Yet, no novel first-in-class antibiotics targeting gram-negative bacteria have been discovered in decades. Our research is dedicated to advancing antimicrobial drug discovery, spanning the spectrum from early-stage target validation to in-depth characterization of promising compounds. We develop rapid and predictive high-throughput screening (HTS) tools—utilizing bacterial bioreporters—and apply integrated target- and cell-based approaches in our screening campaigns. In addition, we create sophisticated phenotypic cell models and examine the impact of novel antimicrobial candidates on host–pathogen dynamics through multi-species co-culture systems and in vivo. A central focus of our work is the inclusion of natural products (NP) and NP-inspired synthetic compounds in our screening strategies, promoting their effective incorporation into HTS workflows.
We belong to the Drug Research Program and the Division of Pharmaceutical Biosciences at the Faculty of Pharmacy. We are also hosting the Bioactivity Screening Unit, which provides researchers access to screening instrumentation as well as consultation in matters such as compound libraries, screening assay development and quality control relevant for screening campaigns. This unit belongs to the Drug Discovery and Chemical Biology network, and is a HiLIFE infrastructure facility, and EU-OPENSCREEN partner site.
More specifically, our research themes are:
Our aim is to discover novel antimicrobial compounds against the most critical bacteria, such as ESKAPE pathogens and Enterobacteriaceae, which pose a high risk due to increasing resistance. We also strive to identify and characterize compounds effective against bacterial biofilms, commonly associated with chronic infections. To support this, we develop predictive, real-time screening methods—employing, for example, bioluminescent bacterial strains—and methodologies that enable miniaturization and automation of screens. One major limitation in the development of new antimicrobials is the lack of efficient techniques for characterizing active compounds identified in the primary screening stage. Therefore, our objective is also to advance promising candidates through a comprehensive set of follow-up studies, including mode-of-action and in vivo experiments. We believe that predictive phenotypic screening strategies, an effective panel of follow-up assays, and tools for pathway and mode-of-action analysis will provide a strong foundation for improving success rates in antimicrobial drug discovery.
Pathogens deploy a range of virulence factors to evade host defense mechanisms and cause harm. Antivirulence therapies—which target the molecular mechanisms behind virulence—offer an innovative and promising alternative to traditional antibiotics. One of the most compelling aspects of antivirulence agents is that they do not inhibit bacterial growth, thereby avoiding the selective pressures that drive bacterial evolution and resistance. A key focus of our research is bacterial quorum sensing (QS)—a form of cell-to-cell communication via chemical signals—which regulates the expression of many virulence factors. We explore under-investigated targets linked to bacterial virulence and screen for inhibitors that could interfere with these processes. Additionally, we investigate a common virulence trait among several E. coli pathovars: host cell adhesion. To study this interaction in depth, we develop host–pathogen co-culture models that enable close examination of how bacteria engage with host cells. By thoroughly assessing the impact of antivirulence strategies, we aim to show their potential as game-changers in the development of entirely new classes of antibacterials—and to contribute to a paradigm shift in infectious disease treatment.
Despite significant advances in synthetic chemistry and high-throughput screening (HTS) technologies, natural products continue to play a vital role in drug discovery. Their distinct chemical structures and unique biological activities often surpass what can be achieved with purely synthetic compounds. Many natural products also have a rich history of use in traditional medicine, offering valuable insights into their safety and therapeutic potential. However, turning newly discovered natural products into viable drug candidates remains a challenge. That’s why we place special emphasis on integrating natural products (NP) and NP-inspired synthetic compounds into our screening efforts—ensuring they are effectively incorporated into HTS campaigns.