- >100 small molecules designed and synthesized to target the AI-2 quorum sensing pathway
- Novel LsrK inhibitors identified through structure-based and multidisciplinary approaches
- Effective inhibition of biofilm formation in major pathogens (S. aureus, E. coli, P. aeruginosa)
- Antivirulence activity without affecting bacterial growth, reducing pressure for resistance development
The project has established a fully integrated drug discovery platform combining computational modeling, medicinal chemistry, and experimental validation for the identification of small-molecule modulators of bacterial quorum sensing.
Structure-based approaches enabled the discovery of novel LsrK-targeting ligands, providing new chemical starting points to interfere with the AI-2 signaling pathway, a key regulator of interspecies bacterial communication.
More than 100 compounds have been designed and synthesized through complementary strategies, including hit optimization, scaffold-hopping, and substrate-inspired design, significantly expanding the chemical space associated with LsrK recognition.
Biological evaluation identified multiple compounds capable of inhibiting biofilm formation across both Gram-positive and Gram-negative pathogens, including Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
Importantly, the most active molecules were shown to attenuate virulence-related phenotypes without affecting bacterial growth, confirming their antivirulence mechanism and their potential to reduce selective pressure for resistance.
The robustness of the approach is supported by peer-reviewed publications in high-impact journals, providing a solid proof-of-concept for targeting bacterial communication as a strategy for the development of next-generation anti-infective therapies.