Background
Antimicrobial resistance is rapidly undermining the effectiveness of traditional antibiotics and represents one of the most pressing challenges for global health. Conventional antibacterial therapies are designed to kill bacteria or inhibit their growth. While highly effective, these strategies exert strong selective pressure on microbial populations, often accelerating the emergence and spread of resistant strains.
In response to this growing crisis, increasing attention has been directed toward antivirulence approaches, which aim to disarm pathogenic bacteria rather than eliminate them. By interfering with the molecular mechanisms that regulate virulence, it may be possible to reduce the severity of infections while minimizing the evolutionary pressure that drives antibiotic resistance.
Among the emerging targets for antivirulence therapies, bacterial communication systems have attracted particular interest.
Project Focus
Many bacteria coordinate collective behaviours through a chemical communication process known as quorum sensing. Through the production and detection of small signalling molecules, bacterial populations can regulate gene expression in a cell-density dependent manner. These signalling networks control several key processes associated with pathogenicity, including toxin production, host colonization, and biofilm formation.
This project specifically focuses on the AI-2 mediated quorum sensing system, a signaling pathway that enables communication not only within a single bacterial species but also across different species. Because of its central role in bacterial coordination, the AI-2 pathway represents an attractive target for the development of innovative antivirulence strategies.
Research Strategy
The project adopts an integrated medicinal chemistry and chemical biology approach aimed at identifying small molecules capable of interfering with AI-2 mediated signaling.
The research activities combine computational and experimental methods, including structure-based design, chemical synthesis of novel compounds, biophysical studies of protein–ligand interactions, and microbiological assays evaluating the effects of candidate molecules on biofilm formation and virulence-associated phenotypes.
This multidisciplinary workflow allows the systematic exploration of the chemical space compatible with AI-2 signaling proteins and supports the identification of compounds capable of modulating bacterial communication pathways.
Expected Impact
By targeting bacterial communication rather than bacterial viability, this project aims to contribute to the development of next-generation anti-infective strategies. Compounds that interfere with quorum sensing could reduce bacterial virulence and biofilm formation while exerting lower selective pressure for resistance compared to traditional antibiotics.
In the long term, this approach may open new opportunities for innovative therapeutic strategies capable of complementing existing antimicrobial treatments and contributing to the global effort to combat antimicrobial resistance.