Fredrik Almqvist Lab

The research group is focused on the design and synthesis of biologically active compounds against infectious and neurodegenerative diseases. Currently, the group focuses on designing and synthesizing new peptidomimetics to fight antibiotic-resistant bacteria including Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). We have also developed compounds that make the tuberculosis bacterium Mycobacterium tuberculosis sensitive to immune responses and certain antibiotics again.

In collaboration with research groups in Europe and the United States, the effects of these compounds are being studied in vitro and in vivo models and studies to understand the exact mechanisms of action. The projects are interdisciplinary with collaborations across different fields of research.  We have also developed substances that selectively inhibit the pathogenic cascade of Chlamydia trachomatis as well as substances that attenuates Listeria monocytogenes virulence.

Fredrik Almqvist lab has pioneered the design and synthesis of ring-fused 2-pyridone compounds as peptidomimetics and together with Dr. Hultgren’s lab at Washington University in St. Louis we have shown that these mimetics are ideal for the development of antivirulence compounds. We have developed small molecules called “pilicides” that inhibit chaperone-usher pathway (CUP) pili, which are important virulence factors of uropathogenic E. coli (UPEC) and this has resulted in a deeper understanding of regulation of CUP pili biosynthesis and the ability of UPEC to establish biofilm formation. In addition, together with Dr. Chapman at the University of Michigan we have further studied a subset of the pilicides called “curlicides” that dependent upon the substitution pattern on the central fragment have the ability to affect curli assembly in E. coli. These compounds are excellent tools in the strive for a greater understanding of the mechanisms behind amyloid assembly in general but curli assembly in particular.

Both pili and curli are important constituents in different bacterial biofilms and the group has a general interest in developing biofilm inhibitors. In this context Fredrik Almqvist started a collaboration with Dr. Christina Stallings at Washington University in St. Louis to develop their discovery of mycobacterial tolerance inhibitors (MTIs) and investigate and understand the exact mode of action of the MTIs. These new compounds have great potential to improve treatment regimens for Tuberculosis, the deadliest infectious disease in the world. The wide range of inhibitors that have been developed in the lab has led to several cross disciplinary collaborations and among these FA has ongoing research with UCMR researchers Dr. Sven Bergström and Åsa Gylfe (Chlamydia), Jörgen Johansson and Elisabeth Sauer-Eriksson (Listeria) and Johan Normark (Tuberculosis) with the aim to improve efficacy and dissect exact mode of action.