Projects / Programmes source: ARIS

Molekulski mehanizem sprožitve proteazne aktivnosti bakterijskega represorja LexA (Slovene)

Research activity

Code Science Field Subfield
4.06.04  Biotechnical sciences  Biotechnology  Microbe biotechnology 

Code Science Field
2.11  Engineering and Technology  Other engineering and technologies 
Evaluation (rules)
source: COBISS
Researchers (14)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  13654  PhD Jerneja Ambrožič Avguštin  Biochemistry and molecular biology  Researcher  2010 - 2012  253 
2.  15686  PhD Gregor Anderluh  Biochemistry and molecular biology  Researcher  2009 - 2011  968 
3.  30435  Gregor Bajc    Technical associate  2009 - 2012  36 
4.  26491  PhD Maruška Budič  Biochemistry and molecular biology  Researcher  2010 - 2011  24 
5.  24290  PhD Matej Butala  Biochemistry and molecular biology  Researcher  2011  236 
6.  25518  PhD Miha Črnigoj  Pharmacy  Researcher  2011 - 2012  44 
7.  09836  PhD Blagajana Herzog-Velikonja  Biochemistry and molecular biology  Researcher  2009 - 2012  120 
8.  30736  PhD Simona Kamenšek  Medical sciences  Junior researcher  2009 - 2012  15 
9.  20788  PhD Lejla Pašić  Biochemistry and molecular biology  Researcher  2009 - 2012  88 
10.  29420  PhD Živa Petkovšek  Microbiology and immunology  Junior researcher  2009 - 2012  26 
11.  15328  PhD Kristina Sepčić  Biochemistry and molecular biology  Researcher  2009 - 2011  728 
12.  23963  PhD Silva Sonjak  Biotechnology  Researcher  2009 - 2011  58 
13.  16064  PhD Marjanca Starčič Erjavec  Biochemistry and molecular biology  Researcher  2009 - 2012  441 
14.  07042  PhD Darja Žgur Bertok  Biochemistry and molecular biology  Head  2009 - 2012  441 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  66,215 
Significance for science
The SOS response is in bacteria induced by stress provoked by DNA damage and arrest of DNA replication. Even though the SOS response was first described in 1974, the molecular mechanisms involved in induction of the response are still unresolved. Recent studies have revealed that the SOS response controls, besides DNA repair, also the development and dissemination of antibiotic resistance. Among the most problematic are Enterobacteria, Staphylococcus aureus and C. difficile. The latter has been designated by the media a "superbacteria", and with regard to mortality already surpasses methicillin resistant S. aureus (MRSA). The key regulators of the SOS response are protein RecA, the activator and the repressor, LexA. Our work was first to resolve the structure of the DNA bound LexA protein and that of LexA enabling self cleavage which is required for induction of the SOS response. Our results have provided important insight into the SOS system upgrading the current model of the SOS response. In collaboration with dr. Maja Rupnik, we were first to initiate studies of the SOS resposne of C. difficile. The latter is one of the most common causative agents of nosocomial intestinal infections. As we showed that, the E. coli RecA* protein, induces self-cleavage of LexA or DinR (C. ciffficile homolof of LexA) our results indicate that, the SOS response is widely conserved among bacteria. Employing in silico analysis, we were first to determine 15 potential DinR operator sites in the C. difficile genome. The operator sites were confirmed employing SPR and subsequently, a DinR DNA binding motif was constructed for C. difficile.
Significance for the country
Successful treatment of bacterial infections and prevention of the dissemination of antibiotic resistances requires the use of efficient antimicrobial agents. Due to the prevalence of antibiotic resistance determinants, in Slovenia as well as elsewhere, consecutive treatment with several different antibiotics as well as with combinations of antibiotics has become frequent. More frequent is hospitalization which markedly increases health care costs, affects the quality of life and additionally endangers other hospitalized patients. A marked increase in mortality due to antibiotic therapy associated infection with Clostridium difficile, provoking pseudomembranous colitis, has also been established. Urgently needed are new approaches and new targets of antimicrobial agents. Discovery and use of substances which inhibit mechanisms provoking antibiotic resistance, as for example the SOS system, will also prolong the efficacy of clinically significant traditional antibiotics. Novel approaches such as, crystalography and modelling of target proteins, allow for more rapid and efficient quests for appropriate targets and their inhibitors. The results of our research project elucidate the molecular mechanism of self cleavage of the LexA protein. On the basis of our research and in collaboration with the Faculty of Pharmacy, new antibiotic substances which inhibit the SOS response are already being developed and tested. Additionally, our results were published in a journal ranking at the top of the field (Nucleic Acids Research, IF=8,026), placing Slovene science on a global scale, at a level comparable with the best.
Most important scientific results Annual report 2009, 2010, 2011, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2009, 2010, 2011, final report, complete report on dLib.si
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