Uncovering the hidden role of bacterial microRNAs in chronic respiratory diseases

Understanding the mechanisms through which bacteria interact with the human body and contribute to the progression of chronic respiratory diseases is the aim of the research led by Dr. Laura Veschetti, Infections and Cystic Fibrosis Unit, winner of the 2023 call “Biomedical research conducted by young researchers” promoted by Fondazione Cariplo, with the project Unravelling the impact of Pseudomonas aeruginosa microRNAs on microbe-host interaction and drug response in chronic respiratory diseases.

Chronic lung diseases, including bronchiectasis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, are among the leading causes of illness and mortality worldwide. Their treatment is often complicated by persistent lung infections, frequently sustained by bacteria such as Pseudomonas aeruginosa, which is able to evade immune defenses and develop resistance to drugs.

In recent years, a new player has emerged: microRNAs (miRNAs). Not only does the human body produce these regulatory molecules, which are essential for immune and inflammatory responses, but bacteria can also release miRNAs capable of communicating with human cells. This largely unexplored territory is at the core of the project led by Dr. Veschetti.

“Our goal,” explains the researcher, “is to investigate the role of miRNAs produced by Pseudomonas aeruginosa during chronic respiratory infections. The underlying idea is that these small bacterial RNAs may modulate the host immune response, influence inflammatory processes, and even affect the effectiveness of therapies.”

To achieve this, the team combines bioinformatic and experimental approaches. On the one hand, miRNAs produced by P. aeruginosa under infection conditions are analyzed using big data analysis tools to identify potential human target molecules. On the other hand, the most promising interactions are validated in the laboratory and correlated with clinical data from patients affected by chronic respiratory diseases.

This integrated approach serves a dual purpose: improving the understanding of the complex mechanisms regulating host–pathogen interactions, and identifying new therapeutic targets that could pave the way for innovative drugs or personalized strategies to combat chronic respiratory infections.

“If we confirm that bacterial miRNAs play an active role in modulating the disease,” emphasizes Dr. Veschetti, “we will gain a new perspective on chronic respiratory infections. This would not only enhance our understanding of the biological mechanisms underlying these conditions, but also open the door to more effective and targeted therapies, truly capable of improving patients’ lives.”

Receiving funding from Fondazione Cariplo has had a profound personal and professional significance for Dr. Veschetti.

“This is my first grant as a young Principal Investigator,” she explains, “and it represents an important recognition. Fondazione Cariplo provides the resources needed to pursue my research independently, and knowing that international experts considered the project innovative and promising has been a great encouragement. This support is valuable not only as recognition of current work, but also as a solid foundation for developing future projects and contributing to the understanding of chronic lung diseases.”