Browsing by Subject "faagihoito"

The increase of antibiotic resistance is one of the major healthcare threats globally. One potential way to battle against antibiotic resistant bacterial infections is to treat them with the natural opponents of bacteria, bacteriophages, known as phage therapy. The aim of this thesis was to identify new bacteriophages against clinically notable bacterial species such as Escherichia coli, Burkholderia cepacia, Enterococcus faecalis and Enterococcus faecium. Bacteriophages were screened from various origins such as hospital sewage samples, soil samples and manure samples, collected in between 2019 and 2022. The isolated bacteriophages were then initially characterized to evaluate their potential use in phage therapy. In this thesis, two phages (fHo-Eco16, fHo-Eco17) against clinical E. coli isolate and one phage (fHo-Efa06) against clinical E. faecalis isolate were found from the recently collected Finnish hospital sewage sample pool. Both E. coli phages were classified as Felixounaviruses belonging to family of Ounavirinae and class of Caudoviricetes. Enterococcus phage fHo-Efa06 was characterized as Saphexavirus belonging to class of Caudoviricetes. Preliminary genome annotation did not reveal any characteristics of lysogenic lifecycle, or antibiotic resistance or bacterial toxin genes, which would prevent the use of phages in phage therapy. Both E. coli phages (fHo-Eco16, fHo-Eco17) showed narrow host range infecting only the primary host bacterial isolate but none of 29 other tested clinical E. coli isolates. Phage fHo-Efa06 showed relatively broad host range properties infecting nine tested E. faecalis isolates out of 20 tested E. faecalis isolates but no infection capabilities against six tested clinical E. faecium isolates. In conclusion, freshly collected hospital sewage seemed to be optimal environment to find bacteriophages against clinical bacterial isolates. Furthermore, phages fHo-Eco16, fHo-Eco17 and fHo-Efa06 did not display any strictly unsuitable properties which could prevent their use in phage therapy. In turn, to obtain the definitive certainty on the usability of the phages in therapeutic use, in-depth host range screening together with detailed functional and structural annotation for the phage genomes of fHo-Efa06, fHo-Eco16 and fHo-Eco17 should be completed.

Antibiotic-resistant bacterial infections are a silently spreading pandemic that endangers public health and the healthcare system globally. Common infections may become more life-threatening, and hospital-acquired multi-drug-resistant infections soon compromise all medical procedures, such as surgeries and chemotherapy treatments. Two major players affecting the effectiveness of antimicrobial therapy against polymicrobial infections are interactions between bacterial species and biofilm formation. Bioiflm-embedded cells are protected from various threats, such as the host immune system and antibiotic interventions in the commensal polymicrobial community of increased virulence. Given the increasingly limited options of antibiotics against biofilm-associated antimicrobial-resistant infections, novel therapeutic strategies are needed. Phage therapy has regained interest as a promising strategy for treating antibiotic-resistant bacterial infections and limiting the evolution of resistance. In particular, phage-antibiotic combination therapy has been shown to be more efficient in treating pathogenic bacteria than using either one alone. In this study, I aimed to find a phage-antibiotic combination therapy against the formation of single and dual-species biofilm of S. aureus and P. aeruginosa and demonstrate the therapeutic potential of phages in combination with antibiotics by using a simple but clinically relevant in vitro biofilm model that supports the concomitant growth of P. aeruginosa and S. aureus. I found out that using phage Stab21 with ciprofloxacin or vancomycin alone or in combination was more effective in preventing the biofilm formation of S. aureus than using phage or antibiotic therapy alone. This was observed in the single-species biofilm of S. aureus and the dual-species biofilm in coculture with P. aeruginosa. Even though Stab21 alone could not infect S. aureus in liquid culture, adding ciprofloxacin or vancomycin at sublethal concentrations increased phage production.

The objective of this thesis was to isolate and characterized phages from Beninese wastewater samples against clinical Acinetobacter baumannii strains for phage therapy use. A. baumannii is one of the most threatening nosocomial bacteria because most of the strains are resistant towards all commonly used antibiotics. One promising alternative treatment method could be phage therapy that utilizes lytic phages to dispose of specific bacteria. In this thesis, seven phages infecting clinical A. baumannii strains were isolated and two of them were characterized more in detail. Phages vB_AbaA_fBenAci001 (fBen-Aci001) and vB_Aba_fBenAci002 (fBen-Aci002) were members of the Friunavirus genus of the Autographiviridae family. In addition, they were the only phages characterised from their respective species to date. The genome analysis revealed 82.2% identity between the phages. No genes indicating lysogenic lifecycle, or genes encoding bacterial toxins or antibiotic resistance were identified from either of them. Phage fBen-Aci001 were infecting 4% and fBen-Aci002 were infecting 9% of tested 23 clinical A. baumannii isolates. Phylogenetic tree which was constructed based on whole genome sequences was compared to the trees that were made using tailspike proteins and capsid proteins. No correlation between genome-wide tree and trees built based on single genes were seen. In conclusion, the Beninese hospital wastewater appeared to be a good source for A. baumannii phages, as several phages were isolated and they were infecting clinical multidrug resistant strains isolated from Finnish patients. Phages fBen-Aci001 and fBen-Aci002 were concluded to be potential candidates to be used in the phage therapy though the narrow host range might negatively affect their usability.