Browsing by Author "Pankka, Salla"

The objective of this thesis was to isolate and characterize new bacteriophages (phages) against clinical Klebsiella pneumoniae strains for phage therapy. K. pneumoniae is causing an emerging threat to global health due to its broad antibiotic resistance profile and hypervirulent strains. New treatment options are urgently needed to defeat the crisis. Phage therapy could provide one option to treat multiresistant K. pneumoniae infections. In this thesis, five new phages were isolated and characterized from Finnish wastewater and Georgian river water against two clinical K. pneumoniae strains. The three phages from Georgian river water, fMtkKpn01, fMtkKpn03, and fMtkKpn04, resembled Drulisviruses based on phylogenetic analysis. The two phages from Finnish wastewater, fJoKpn03 and fJoKpn05 were phylogenetically distinct. fJoKpn03 couldn’t be classified. fJoKpn05 resembled Weberviruses. Based on sequence analysis, none of the phage genomes included any harmful genes that would prevent their use in phage therapy. All phages demonstrated a 6-hour total inhibition to host bacterial growth. Their host range was determined to be narrow, only infecting their respective host strains from the 80 bacterial strains tested. All the phages tolerated high pH well. fJoKpn03 was the only one tolerating very low pH. All phages showed a synergistic effect on the inhibition of bacterial growth when applied together with piperacillin. In conclusion, all five phages proved potential for phage therapy. They demonstrated inhibitory action against K. pneumoniae strains with capsule types against which there previously were no phages in our collection. Due to their narrow host range, they could be suited for personalized phage therapy or used in combination therapy with antibiotics to increase efficacy and duration of action. fJoKpn03 could provide an opportunity for oral administration due to its broad pH stability profile.