ИСТИНА

The emergence of microbes that are able to resist most of the antibiotics used in clinical practice (multidrug-resistant organisms) is a crucial challenge for medical community. One of the possible solutions is to search for new, more powerful antimicrobials that would be able to defeat current resistance. We have developed in vivo system for this search. The system is represented by E.coli BW25113 ∆tolC strain with the plasmid carrying genes of two fluorescent proteins, RFP and Katushka2S. The construction of plasmid is such that RFP expression is dramatically increased under exposure to SOS-response inducing compound; the expression of Katushka2S rises in the presence of a ribosome-stalling agent. At the present moment, the reporter system has been successfully applied in the screening of several tens of thousands of compounds for their antimicrobial activity. One of our current aims is to state mechanism of action of tetracenomycine X (tetX), a compound we found in screening. In literature it is described as a possible DNA-damaging agent; however, our system indicates that tetX possesses translation inhibitory activity. We have found that tetX inhibits translation in vivo and in vitro. We have also succeeded in obtaining mutants that were resistant to tetX. This mutant strain has been found to have the mutation in 23S rRNA in ribosomal tunnel.