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Projects / Programmes source: ARRS

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
Points
4,618.92
A''
482.33
A'
1,952.15
A1/2
3,232.42
CI10
5,353
CImax
324
h10
35
A1
16.13
A3
32.38
Data for the last 5 years (citations for the last 10 years) on June 5, 2023; A3 for period 2017-2021
Data for ARRS tenders ( 04.04.2019 – Programme tender, archive )
Database Linked records Citations Pure citations Average pure citations
WoS  379  7,633  6,308  16.64 
Scopus  410  9,319  7,670  18.71 
Researchers (21)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  54374  PhD Urban Bezeljak  Natural sciences and mathematics  Researcher  2021 - 2022  14 
2.  55064  Lara Bolčina  Natural sciences and mathematics  Researcher  2021 - 2023  11 
3.  52971  Tina Brecelj  Biotechnical sciences  Researcher  2020 - 2022 
4.  11308  PhD Andrej Cör  Medical sciences  Researcher  2020 - 2023  387 
5.  38672  PhD Klemen Čamernik  Natural sciences and mathematics  Researcher  2020  21 
6.  36410  Tadej Furlan  Medical sciences  Researcher  2020 - 2023  17 
7.  53966  Klara Gregorič  Biotechnical sciences  Researcher  2020 
8.  56352  Monika Marušić  Biotechnical sciences  Researcher  2022 - 2023 
9.  33035  PhD Rene Mihalič  Medical sciences  Researcher  2020 - 2023  101 
10.  51415  Petra Modic  Biotechnical sciences  Researcher  2020 - 2021 
11.  52213  Rok Mravljak  Biotechnical sciences  Researcher  2022 - 2023  18 
12.  16327  PhD Matjaž Peterka  Biotechnical sciences  Researcher  2020 - 2023  216 
13.  12728  PhD Aleš Podgornik  Engineering sciences and technologies  Principal Researcher  2020 - 2023  681 
14.  12684  PhD Helena Podgornik  Medical sciences  Researcher  2020 - 2023  329 
15.  29594  PhD Katarina Reberšek  Medical sciences  Researcher  2020 - 2023  34 
16.  50036  PhD Metka Stantič  Natural sciences and mathematics  Researcher  2020 - 2021 
17.  50139  Katja Šivec  Engineering sciences and technologies  Researcher  2021 
18.  35429  PhD Katja Šuster  Medical sciences  Researcher  2020 - 2023  20 
19.  23524  PhD Rihard Trebše  Medical sciences  Researcher  2020 - 2023  386 
20.  37945  Jasmina Tušar  Natural sciences and mathematics  Researcher  2021 
21.  32306  PhD Janja Zupan  Medical sciences  Researcher  2021 - 2023  105 
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  22,060 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  73,881 
3.  0355  Orthopaedic Hospital Valdoltra  Ankaran  5053765  2,195 
4.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  16,356 
5.  3030  Center of Excellence for Biosensors, Instrumentation and process Control  Ajdovščina  3660460  904 
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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