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Projects / Programmes source: ARIS

EFFICACY OF BACTERIOPHAGES FOR TREATEMENT OF EXTRACELULAR AND INTRACELULAR BACTERIAL INFECTIONS OF IMPLANTANTS

Research activity

Code Science Field Subfield
4.06.04  Biotechnical sciences  Biotechnology  Microbe biotechnology 
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
3.04  Medical and Health Sciences  Medical biotechnology 
3.01  Medical and Health Sciences  Basic medicine 
Keywords
bacteriophages, prosthetic joint infections, intracellular bacterial infection, osteoblasts, mesenchymal stem/ stromal cells, biofilms 1.
Evaluation (rules)
source: COBISS
Researchers (22)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  54374  PhD Urban Bezeljak  Biochemistry and molecular biology  Researcher  2021 - 2022  15 
2.  55064  Lara Bolčina  Pharmacy  Researcher  2021 - 2022  12 
3.  11308  PhD Andrej Cör  Oncology  Researcher  2020 - 2023  420 
4.  38672  PhD Klemen Čamernik  Pharmacy  Researcher  2020  21 
5.  36410  Tadej Furlan  Microbiology and immunology  Researcher  2020 - 2023  17 
6.  53966  Klara Gregorič  Biotechnology  Researcher  2020 
7.  52971  Tina Kobal  Biotechnology  Researcher  2020 - 2022 
8.  19649  PhD Marija Nika Lovšin  Microbiology and immunology  Researcher  2023  126 
9.  56352  Monika Marušić  Microbiology and immunology  Researcher  2022 - 2023  10 
10.  33035  PhD Rene Mihalič  Neurobiology  Researcher  2020 - 2023  121 
11.  51415  Petra Modic  Biotechnology  Researcher  2020 - 2021 
12.  52213  PhD Rok Mravljak  Biotechnology  Researcher  2022 - 2023  26 
13.  16327  PhD Matjaž Peterka  Biotechnology  Researcher  2020 - 2023  226 
14.  12728  PhD Aleš Podgornik  Chemical engineering  Head  2020 - 2023  713 
15.  12684  PhD Helena Podgornik  Microbiology and immunology  Researcher  2020 - 2023  354 
16.  29594  PhD Katarina Reberšek  Microbiology and immunology  Researcher  2020 - 2023  43 
17.  50036  PhD Metka Stantič  Biochemistry and molecular biology  Researcher  2020 - 2021  10 
18.  50139  Katja Šivec  Chemical engineering  Researcher  2021 
19.  35429  PhD Katja Šuster  Neurobiology  Researcher  2020 - 2022  48 
20.  23524  PhD Rihard Trebše  Neurobiology  Researcher  2020 - 2023  439 
21.  37945  Jasmina Tušar  Biochemistry and molecular biology  Researcher  2021  10 
22.  32306  PhD Janja Zupan  Metabolic and hormonal disorders  Researcher  2021 - 2023  111 
Organisations (5)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0103  University of Ljubljana, Faculty of Chemistry and Chemical Technology  Ljubljana  1626990  23,454 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,953 
3.  0355  Orthopaedic Hospital Valdoltra  Ankaran  5053765  2,428 
4.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,415 
5.  3030  Center of Excellence for Biosensors, Instrumentation and process Control  Ajdovščina  3660460  299 
Abstract
Goal of the proposed project is to investigate possibility of bacteriophage therapy in periprosthetic joint infections (PJI) treatment. The number of joint implants is increasing every year, as they nearly eliminate pain and contribute significantly to better mobility of the patients affected with end stage joint derangements. Along with increasing number of patients with joint replacements, the associated complications increase as well. They occur in slightly less than 10% of patients, with the largest proportion representing aseptic failures of the joint prostheses. Rarer but significantly more dangerous complications are PJI since they pose a great health risk for patients as they cause pain, reduced mobility, and failure of the artificial joint, in the worst cases even loss of patient's limb or even death. Chronic PJI are the most difficult ones. Their treatment is complicated due low bacterial cell concentration or their particular physiological state with low metabolic activity, making proper diagnosis challenging. In many chronical PJI bacteria grow in biofilms but in some cases they probably also internalize human cells (e.g. osteoblasts), in both cases causing significantly reduced antibiotic efficacy. During the proposed project we will focus on a treatment of bacterial strains of S. aureus, S. epidermitis and C. acnes, being the most common source of PJI. Appropriate bacteriophages that are able to efficiently lyse selected bacterial strains during their exponential growth will be chosen. All selected bacteria are also able to form biofilm, consisting of extracellular polysaccharides and bacterial cells in different physiological states. To investigate efficiency of bacteriophage treatment on bacteria in defined physiological state, a continuous cultivation system will be used allowing to accurately estimated bacteriophage growth parameters such as burst size, latent period and adsorption constant and through them indirectly estimate efficiency of phage therapy. Obtained results will be compared with results treating with bacteriophages biofilms formed under different conditions. Furthermore, efficiency of bacteriophages on bacteria being in viable but non culturable (VBNC) physiological state will be examined. Substantial efforts will be dedicated to investigate effect of bacteriophages on bacteria internalizing human cells, involved in prosthetic joints osteointegration like mesenchymal stem/ stromal cells and primary osteoblasts. Penetration of bacteriophages into primary human cells will be investigated as well as the effect of bacterial physiological state on internalization of primary human cells. Finally, effect of bacteriophage treatment on internalized bacterial cells will be investigated. Throughout the project the following goals will be accomplished: · - To determine effect of physiological state (including VBNC) of planktonic bacteria cells S. aureus, S. epidermitis in C. acnes on lytic bacteriophage efficiency · - To determine efficiency on bacteriophages for treatment of biofilms formed by selected bacteria species · - To determine bacteriophages being able to penetrate into primary human cells · - To determine effect of bacteria physiological state on their ability to penetrate into primary human cells (intracellular infection) · - To determine bacteriophage efficiency in treatment of primary human cells intracellular infection - Based on obtained results to propose an algorithm of PJI treatment using bacteriophages that can serve as basis for further clinical tests.
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