New antibacterial compounds developed at University of Eastern Finland

Researchers in Finland have developed new antibacterial compounds for potential future use in drug development.

A team from the University of Eastern Finland focused on the role of the LsrK kinase protein, its role in bacterial communication, and how it can be used as a potential target in antibacterial drug design.

The researchers built the first 3D model of the LsRK protein and then performed virtual screenings of selected compounds against the protein.

In particular, the team focused on a process of bacterial communication called quorum sensing (QS), which involves the host colonisation, virulence factors production, biofilm formation and infection establishment.

A new strategy for developing antivirulence agents involves interfering with the production and processing of QS mediators. To do this, the researchers inhibited LsRK leading to the inactivation of QS and hindering the development of the disease.

QS is mediated by signalling molecules called autoinducers (AI) in a population density dependent manner. The AI-2 signalling molecule is involved in the way bacteria communicates with others of their own species (intraspecies), as well as bacteria of a different species (interspecies).  

In a press statement, the team said: “The identified LsrK inhibitors through this study are the first class of LsrK inhibitors reported to date. These hits will be further optimized to achieve high affinity and function as useful tools for improving our understanding towards inhibition of LsrK in the AI-2 pathway and its significance as a potential antivirulence strategy”.

“Considering the limited knowledge about LsrK structure, our study offers a great overview of the behaviour of the protein and a perfect starting point to better understand the protein-substrate dynamics and how to interfere with it.”