Development of recombinant endolysins conjugated with nanoparticles for the treatment of topical bacterial infections

• Κύριος συγγραφέας: Al-Waeel, Mansoor
• Άλλοι συγγραφείς: Αντιμησιάρη, Σοφία
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Antimicrobial resistance; Endolysines; Phage therapy; Recombinant proteins; Αντιμικροβιακή αντίσταση; Ενδολυσίνες; Θεραπεία φάγων; Ανασυνδυασμός πρωτεϊνών

Antimicrobial resistance (AMR) is an alarming crisis and it could cause huge impacts on global health, development, and economy. Studies have estimated that the death toll from AMR could reach 10 million deaths annually by 2050. These data highlight the dire need to tackle this problem in the near future especially for the pathogens with multidrug resistance. Phage therapy is based on the capacity of bacteriophages to kill bacteria. For decades it has been used as an alternative to conventional antibiotic therapy in several countries. Endolysins are the lytic enzymes that are used by phages to lyse and exit the infected bacterial cell. Because of unlikely induction of drug resistance and fine strain specificity, endolysins could be the next generation antibiotics to fight multidrug-resistant bacteria. We cloned and expressed recombinant endolysins that could be used in the treatment of gram-negative and gram-positive multidrug-resistant bacterial infections. The proteins were tested for integrity, purity and in vitro biological activity. To design a delivery system that might be suitable for the treatment of skin infections, several polymeric- and lipidic-based nanomaterials were investigated for conjugating and/or encapsulating the lytic enzymes. The developed nanomaterials were characterized for their size and zeta potential as well as for their antibacterial activity. The formulations showing the best results in vitro were selected for further in vivo studies and included in protocols addressing release kinetics and stability.