The increase in bacterial pathogens resistant to multiple antibiotics is a major health problem. Since new antibiotics are not easy to find, much of the research is focused on finding ways to increase the effectiveness of already known antibiotics. At subinhibitory concentrations, many antibiotics induce DNA damage in bacteria. In response to the damaged DNA, bacteria initiate a SOS response in which they first produce enzymes that precisely repair the DNA. In the case of severe DNA damage, and later in the SOS response, if the DNA damage has not been repaired, synthesis of error-prone DNA polymerases occurs that support replicative bypass of damaged bases that arrest high-fidelity repair. Mutations introduced into the bacterial genome in this manner can lead to the development of antibiotic resistance. For a long time, it was assumed that the transcription factor LexA and the protein RecA were the only regulators of the SOS response. Recently, it was shown that the bacteriophage GIL01 infecting Bacillus thuringiensis serovar israelenis carries a gene for the small protein gp7 that binds directly to the LexA repressor and increases its affinity for target nucleotide sequences. Recognition of the gp7 protein suggested the existence of small proteins that act as coregulators of LexA, providing an additional level of regulation of the SOS response. In this dissertation, we demonstrated that the gp7 protein is a global regulator of gene transcription in the bacterium B. thuringiensis, as it inhibits the transcription of 1.2 % of bacterial genes. Our results show that gp7 is the key factor that inhibits the transition of phage pBtic235, which coexists with GIL01 in the bacterium, into the lytic cycle. Thus, the gp7 protein ensures that the phage GIL01 produces more progeny than the phage pBtic235 after DNA damage. We have elucidated the mechanism of action of the gp7 protein, which, by binding to LexA, reorients the DNA binding domain of the LexA dimer into the conformation required for binding to DNA, which increases the affinity of the LexA repressor for DNA. Our results show that functionally similar proteins, such as the gp7 protein, exist in other bacteria: (i) gp7 homologs of other tectiviruses infecting bacteria from the group Bacillus cereus sensu lato and (ii) the DdrR protein of the bacterium Acinetobater baumannii. Thus, our results suggest the existence of small proteins with a similar function to gp7 in other bacteria as well, which, as co-regulators of LexA and LexA-like proteins, represent an additional level of regulation of gene transcription in the SOS response.
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