Novel WYL domain-containing transcriptional activator acts in response to genotoxic stress in rapidly growing mycobacteria

Abstract

Abstract The WYL domain is a nucleotide-sensing module that controls the activity of transcription factors involved in the regulation of DNA damage response and phage defense mechanisms in bacteria. In this study, we investigated a WYL domain-containing transcription factor in Mycobacterium smegmatis that we termed stress-involved WYL domain-containing regulator (SiwR). We found that SiwR controls adjacent genes that belong to the DinB/YfiT-like putative metalloenzymes superfamily by upregulating their expression in response to various genotoxic stress conditions, including upon exposure to H2O2 or the natural antibiotic zeocin. We show that SiwR binds different forms of single-stranded DNA (ssDNA) with high affinity, primarily through its characteristic WYL domain. In combination with complementation studies of a M. smegmatis siwR deletion strain, our findings support a role of the WYL domains as signal-sensing activity switches of WYL domain-containing transcription factors (WYL TFs). Our study provides evidence that WYL TFs are involved in the adaptation of bacteria to changing environments and encountered stress conditions.