A mechanism for the Survival of Bacteria in the Presence of Antibiotics Explained

Researchers from the Faculty of Chemistry and Chemical Technology of the University of Ljubljana, in cooperation with Belgian researchers, were the first to explain a molecular mechanism governing the regulation of the toxin-antitoxin module, which explains how and why bacterial cells stop their growth and development.


Authors:
San Hadži, Igor Drobnak, Andrej Mernik, Črtomir Podlipnik, Remy Loris, Jurij Lah


Survival of bacterial cells in presence of antibiotics represents a significant problem for treatment bacterial infections. Such cells tolerate antibiotics either because they acquire specific mutations (changed genotype – resistance) or because they can switch into the metabolically calm, dormant state (changed phenotype – persistence). When the concentration of an antibiotic drops, the bacteria “wake up” and resume multiplying, which results in many recurrent and chronic diseases. It is well-known that bacterial cells can halt their metabolism using their own genetic systems, called toxin-antitoxin modules. The researchers from the Faculty of Chemistry and Chemical Technology of the University of Ljubljana (San Hadži, Igor Drobnak, Andrej Mernik, Črtomir Podlipnik, Jurij Lah), in cooperation with Belgian researchers (Remy Loris laboratory), were the first to explain the molecular mechanism governing the regulation of the toxin-antitoxin module, which explains how and why bacterial cells can stop their growth and development. 

The activity of the module depends on the complex regulation of gene transcription. The regulation mechanism was uncovered by  determining structures of different toxin-antitoxin complexes and by studying the respective protein-protein and protein-operator interactions. These results were synthetized in the quantitative model that predicts the regulation of the growth of bacterial cells in stress conditions. This opens possibilities for planned interventions in the functioning of the module and therby controlling the occurrence of bacterial persisters. 

The research, which was mainly the product of ideas of Slovenian researchers, was published in three articles in distinguished international journals (impact factor > 10). 


Source: 1. San Hadži, Andrej Mernik, Črtomir Podlipnik, Remy Loris in Jurij Lah, “The thermodynamic basis of the fuzzy interaction of an intrinsically disordered protein”, Angew. Chem. Int. Ed. 2017, DOI: http://dx.doi.org/10.1002/anie.201707853 (IF 2016 = 11.709, 11/163 chemistry, multidisciplinary)
2. San Hadži, Sarah Haesaerts, Dukas Jurėnas, Kenn Gerdes, Jurij Lah in Remy Loris, “Ribosome-dependent Vibrio cholerae mRNAse HigB2 is regulated by a β-strand sliding mechanism”, Nucleic Acids Res. 2017, 45, 4972. (IF 2016 = 10.162, 14/286 biochemistry & molecular biology)
3. Alexandra Vandervelde, Igor Drobnak, San Hadži, Yann G.-J. Sterckx, Thomas Welte, Henri De Greve, Daniel Charlier, Rouslan Efremov, Remy Loris in Jurij Lah, “Molecular mechanism governing ratio-dependent transcription regulation in the ccdAB operon”, Nucleic Acids Res. 2017, 45, 2937. (IF 2016 = 10.162, 14/286 biochemistry & molecular biology)