Molecular Microbiology Laboratory
Referent: Prof. Silvia Buroni
Co-workers: Dr. Giulia Barbieri, Dr. Andrea Bonacorsi, Dr. Samuele Irudal, Dr. Viola Camilla Scoffone, Dr. Gabriele Trespidi
1. New strategies to fight cystic fibrosis pathogens. The airways of patients with cystic fibrosis (CF) are colonized by different pathogens (including Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cenocepacia). Eradication of these infections is complicated by the intrinsic resistance of these microorganisms to different antibiotics. In this way, the development of novel drugs, but also of different strategies to counteract drug resistance, remains a major issue for the treatment of infectious lung disease, such as that in CF. We are currently pursuing three different ways:
- a. New antibacterial molecules. We found that a benzothiadiazol compound (10126109) is very active against both Gram-negative and -positive bacteria and we identified a mechanism of resistance, which relies on the extrusion of the new drug through an RND transporter. We also identified the mechanism of action and evaluated the toxicity on CF epithelial bronchial cells. New molecules will be synthesized with the aim to find more active compounds to be evaluated in vivo.
- b. Reverse vaccinology as a tool to fight Burkholderia cenocepacia. A well-proved strategy to counteract both infections and the spread of MDR is vaccination. Particularly, the reverse vaccinology approach, starting from the bacterial genome, focuses directly on genes involved in virulence and pathogenesis. We are focusing on extracellular and membrane proteins predicted to induce immune response to identify promising antigen candidates for the development of a vaccine to prevent and cure B. cenocepacia infections.
- c. Inhibition of bacterial adhesion. The compound PDSTP is a non-toxic dispirotripiperazine-based molecule able to impair viral adsorption to negatively charged heparan sulphate proteoglycans expressed at the surface of human cells. Since CF pathogens exploit these host-cell receptors to interact with the host, PDSTP may be active also on them. In this context, the inhibition of bacterial adhesion to human cells seems an attractive alternative to fight CF MDR infections.
2. New antibacterial drugs against the ESKAPE pathogens. Bacteria belonging to the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) group represent a main threat to public health due to their high levels of antibiotic resistance. In this context, our research is focused on the identification, characterization, and pre-clinical assessment of novel antibacterial drugs active against these pathogens, particularly focusing on cell division as new drug target.
- Vadim Makarov (Bakh Institute of Biochemistry, Russian Academy of Science, Moscow, Russia),
- Tom Coenye (University of Gent, Belgium),
- Alessandra Bragonzi (Ospedale San Raffaele, Milano),
- Francesco Imperi (Università di Roma Tre),
- Antonio Coluccia (Università La Sapienza, Roma),
- Marco Fondi (Università di Firenze),
- Paola Sperandeo (Università degli Studi di Milano Statale).