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Projects / Programmes source: ARIS

Pathogenomics and systems biology of new virulence factors in pathogenic bacteria

Research activity

Code Science Field Subfield
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
B230  Biomedical sciences  Microbiology, bacteriology, virology, mycology 

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Keywords
pathogenomics, systems biology, virulence factor, horizontal gene transfer, regulatory genomics, phylogenomics
Evaluation (rules)
source: COBISS
Researchers (11)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  22614  PhD Jana Boben  Biotechnology  Researcher  2012  82 
2.  26491  PhD Maruška Budič  Biochemistry and molecular biology  Researcher  2011 - 2012  24 
3.  15639  PhD Gregor Gunčar  Biochemistry and molecular biology  Researcher  2012 - 2014  262 
4.  05381  PhD Darja Keše  Microbiology and immunology  Researcher  2011 - 2014  268 
5.  30876  PhD Janez Kokošar  Biochemistry and molecular biology  Junior researcher  2011 - 2013  31 
6.  07673  PhD Dušan Kordiš  Biochemistry and molecular biology  Head  2011 - 2014  215 
7.  00412  PhD Igor Križaj  Biochemistry and molecular biology  Researcher  2011 - 2014  726 
8.  20213  PhD Toni Petan  Biochemistry and molecular biology  Researcher  2011 - 2014  177 
9.  20653  PhD Uroš Petrovič  Biochemistry and molecular biology  Researcher  2011 - 2014  292 
10.  04570  PhD Jože Pungerčar  Biochemistry and molecular biology  Researcher  2011 - 2014  320 
11.  24279  PhD Ana Saksida  Microbiology and immunology  Researcher  2013 - 2014  48 
Organisations (3)
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  23,092 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,706 
3.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,236 
Abstract
The objective of this project is to explain the origin, evolution, genome dynamics and biological roles of the new virulence factors in pathogenic bacteria. Successful microbial pathogens have evolved a range of anti-immune strategies to overcome both innate and acquired immunity, which play critical roles in their abilities to cause disease. The ability of pathogenic bacteria to cause disease in a susceptible host is determined by multiple virulence factors acting individually or together at different stages of infection. Recently, we have found that eukayotic cystatins and stefins have been acquired and co-opted by a few bacteria. One of the major roles of horizontally acquired cystatins and stefins in bacteria could be to evade host immunity or to protect them when in close contact with diverse eukaryotic hosts. Our hypothesis is that some pathogenic bacteria have evolved independently by HGT a novel anti-immune strategy (similarly as eukaryotic parasites) to overcome host innate immunity. Horizontally acquired eukaryotic proteinase inhibitors and secreted phospholipases A2 (sPLA2) could function in genomes of pathogenic bacteria in the process of evasion, invasion and dissemination of pathogens. The acquisitions of novel virulence factors for pathogenic bacteria by horizontal gene transfer from eukaryotes is very rare and was not analysed extensively. To unravel the origin, distribution, evolution and genomics of the new virulence factors from pathogenic bacteria and to obtain clues about their functional consequences for the pathogens, we will perform the large and detailed comparative and evolutionary genomic analysis of the new virulence factors in numerous bacterial genomes. By using very extensive comparative genomic analysis we will obtain and characterize all new proteinase inhibitors (85 families of proteinase inhibitors will be analysed) and PLA2s (17 families of PLA2 will be analysed) of eukaryotic origin in more than 1600 bacterial genomes. The genome organization of the new virulence loci, their chromosome locations and their chromosome mobility will be analysed. The origin, distribution and evolution of the new virulence factors in pathogenic bacteria will be explored. De novo acquired regulatory regions of the new virulence factors from pathogenic bacteria will be analysed. Some of the selected new virulence factors from pathogenic bacteria will be functionally and structurally characterized by gene cloning and expression as well as by biochemical analysis of recombinant proteins. Systems biology approaches will be used for exploring protein interactions of new virulence factors with the host immune system. The latest methods and technologies of comparative genomics, phylogenomics, molecular evolution, systems biology and bioinformatics will be used. For the functional and structural characterization of the selected new virulence factors from pathogenic bacteria we will use the latest methods and technologies of biochemistry and molecular biology.
Significance for science
The obtained results are relevant to a number of important questions in pathogenomics, comparative genomics of pathogens, regulatory genomics of pathogens and systems biology of pathogens. We have elucidated numerous questions regarding the new virulence factors from pathogenic bacteria such as their origin, distribution and evolution; genomic organization of the virulence loci, their chromosome locations and their chromosome mobility; regulatory evolution of de novo acquired promoter regions and their biological roles in pathogenic bacteria. Phylogenomic analysis of horizontally acquired proteinase inhibitors and sPLA2s of eukaryotic origin in bacterial genomes provided definitive answer on the origin, distribution, evolution and genomics of new virulence factors from pathogenic bacteria. Biological roles of new virulence factors in pathogenic bacteria have been elucidated by biochemical analysis of recombinant proteins and by systems biology approaches of selected new virulence factors from pathogenic bacteria. The obtained results are important for various scientific fields: comparative genomics, phylogenomics, regulatory genomics, microbiology, immunology, and for regulatory and functional evolution.
Significance for the country
Our original research in the field of genome research has enabled the introduction of new methods and technologies in the fields of genome biology, »in silico« biology, bioinformatics and molecular evolution in Slovenia. We acquire new and practical knowledge, information and skills in the field of comparative and evolutionary genomics. The consequence of our current research work is that Slovenia is now not excluded from the field of genome research. The results of our original research are published in leading scientific journals and presented at international scientific meetings. Theoretical and practical knowledge from the fields of genomics, proteomics and molecular evolution is transferred to the students and young researchers at the University of Ljubljana and IJS. Diploma students and young researchers are trained and educated in the field of genomics; this newly obtained knowledge is transferred into the pharmaceutical industry and to other research institutions. This project was connected to the research on the comparative genomics of bacteria, which is the part of research programme P1-0207.
Most important scientific results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2013, final report, complete report on dLib.si
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