| Project Detail |
Bacteriocin–antibiotic conjugates for overcoming bacterial antibiotic resistance
The emergence of bacterial antibiotic resistance is a growing threat to public health. Pseudomonas aeruginosa can cause infections in humans, particularly in hospital patients, and is especially dangerous for immunocompromised patients as it becomes resistant to nearly all antibiotics available. A natural protein, pyocin S2, is a bacteriocin able to kill several P. aeruginosa strains. The pyocin gets across the cell envelope by hijacking a nutrient transport system of the bacterium. Preliminary results demonstrated the feasibility of the pyocin as a vector for small molecules. Funded by the Marie Sklodowska-Curie Actions programme, the BactDrugConj project aims to develop bacteriocin–antibiotic conjugates to overcome the resistance mechanisms of P. aeruginosa by combining the vector potency of the pyocin and the bacteriotoxicity of known synthetic antibiotics.
Bacterial antibiotic resistance has become a massive threat to the public health. The situation with the opportunistic pathogen P.aeruginosa is particularly worrying because this major cause of nosocomial infections in immunocompromised patients becomes resistant to nearly all antibiotics available. Pyocin S2 is a bacteriocin, a natural protein able to kill several P.aeruginosa strains. The pyocin highjacks a nutrient transport system of the bacteria to get across the cell envelop. My project aims to develop chimeric bacteriocin-antibiotic conjugates to overcome the resistance mechanisms of P.aeruginosa by combining the vector potency of the pyocin and the bacteriotoxic activity of known synthetic antibiotics. Using the bacteriocin as a Trojan horse will be beneficial because: i) the active uptake of the drug; ii) reduced susceptibility to the efflux-mediated resistance; iii) specific targeting the pathogenic bacteria in the presence of healthy commensal microbiota. Preliminary results with organic fluorophores have revealed the feasibility of the pyocin S2-mediated vectorization of small molecules. In my work I will combine synthetic chemistry, biochemistry, microbiology and pharmacology approaches to synthesise defined antibiotic-pyocin conjugates and to create a new class of antibacterial molecules urgently needed in the post-antibiotic era. |
