Title Development and synthesis of plant-derived recombinant biopharmaceutical proteins active against gram-negative pathogenic bacteria /
Translation of Title Augaluose susintetintų farmacinių rekombinantinių baltymų preparatų, aktyvių prieš gramneigiamas patogenines bakterijas, kūrimas.
Authors Paškevičius, Šarūnas
DOI 10.15388/vu.thesis.455
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Pages 131
Keywords [eng] antimicrobial agents ; pseudomonas ; keratitis, bacteriocins ; pyocins
Abstract [eng] Bacteriocins, antibacterial proteins encoded by bacteria, are promising alternatives to antibiotics. This study focuses on the identification, characterization, production, and application of bacteriocins from gram-negative bacteria for the treatment of infections in humans and animals. The study identified putative bacteriocins from Pseudomonas and Stenotrophomonas species, cloned, expressed them in planta, and purified them. All tested bacteriocins demonstrated efficacy in vitro, and selected pyocins showed potential as antimicrobials in vivo. Domain swapping experiments resulted in the development of superior chimeric bacteriocins, demonstrating the potential for engineering bacteriocins with modified or broadened activity spectra. Newly designed chimeric PyoS5-PmnH efficiently treated murine keratitis caused by P. aeruginosa, and intranasally administered S5-PmnH eradicated lung colonization by P. aeruginosa in murine models. These results provide the initial groundwork for developing plant-made bacteriocins as future non-antibiotic pharmaceuticals, with potential for therapeutical use for both humans and animals.
Dissertation Institution Vilniaus universitetas.
Type Doctoral thesis
Language English
Publication date 2023