Abstract
BackgroundThe SOS response including two main proteins LexA and RecA, maintains the integrity of bacterial genomes after DNA damage due to metabolic or environmental assaults. Additionally, derepression of LexA-regulated genes can result in mutations, genetic exchange and expression of virulence factors. Here we describe the first comprehensive description of the in silico LexA regulon in Clostridium difficile, an important human pathogen.ResultsWe grouped thirty C. difficile strains from different ribotypes and toxinotypes into three clusters according to lexA gene/protein variability. We applied in silico analysis coupled to surface plasmon resonance spectroscopy (SPR) and determined 16 LexA binding sites in C. difficile. Our data indicate that strains within the cluster, as defined by LexA variability, harbour several specific LexA regulon genes. In addition to core SOS genes: lexA, recA, ruvCA and uvrBA, we identified a LexA binding site on the pathogenicity locus (PaLoc) and in the putative promoter region of several genes involved in housekeeping, sporulation and antibiotic resistance.ConclusionsResults presented here suggest that in C. difficile LexA is not merely a regulator of the DNA damage response genes but also controls the expression of dozen genes involved in various other biological functions. Our in vitro results indicate that in C. difficile inactivation of LexA repressor depends on repressor`s dissociation from the operators. We report that the repressor`s dissociation rates from operators differentiate, thus the determined LexA-DNA dissociation constants imply on the timing of SOS gene expression in C. difficile.
Highlights
The SOS response including two main proteins LexA and RecA, maintains the integrity of bacterial genomes after DNA damage due to metabolic or environmental assaults
Damage response genes and controls the expression of dozen genes involved in various other biological functions
Our in vitro results indicate that in C. difficile inactivation of LexA repressor depends on repressors dissociation from the operators
Summary
The SOS response including two main proteins LexA and RecA, maintains the integrity of bacterial genomes after DNA damage due to metabolic or environmental assaults. Derepression of LexA-regulated genes can result in mutations, genetic exchange and expression of virulence factors. Organisms have evolved gene regulatory systems to maintain their genetic integrity. The SOS regulatory network is a paradigm for bacterial response to DNA damage which is controlled by a global transcriptional repressor. LexA binds to DNA recognition sequences (operator) positioned near or overlapping the promoter elements of the SOS genes and occludes. Upon DNA damage, RecA polymerizes on single-stranded. Full list of author information is available at the end of the article activated (RecA*) and facilitates self-cleavage of LexA resulting in coordinated expression of SOS genes [1]. LexA represses synthesis of toxins [6,7] and antibiotic resistance determinants [8], controls integron cassette recombination [9] and lateral transfer of virulence factor genes [10], as well as drug resistance genes [11]
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