MsrR is a thiol-based oxidation-sensing regulator of the XRE family that modulates C. glutamicum oxidative stress resistance

Abstract

Background Corynebacterium glutamicum thrives under oxidative stress caused by the inevitably extreme environment during fermentation as it harbors antioxidative stress genes. Antioxidant genes are controlled by pathway-specific sensors that act in response to growth conditions. Although many families of oxidation-sensing regulators in C. glutamicum have been well described, members of the xenobiotic-response element (XRE) family, involved in oxidative stress, remain elusive. Results In this study, we report a novel redox-sensitive member of the XER family, MsrR (multiple stress resistance regulator). MsrR is encoded as part of the msrR-3-mst (3-mercaptopyruvate sulfurtransferase) operon; msrR-3-mst is divergent from multidrug efflux protein MFS. MsrR was demonstrated to bind to the intergenic region between msrR-3-mst and mfs. This binding was prevented by an MsrR oxidation-mediated increase in MsrR dimerization. MsrR was shown to use Cys62 oxidation to sense oxidative stress, resulting in its dissociation from the promoter. Elevated expression of msrR-3-mst and mfs was observed under stress. Furthermore, a ΔmsrR mutant strain displayed significantly enhanced growth, while the growth of strains lacking either 3-mst or mfs was significantly inhibited under stress. Conclusion This report is the first to demonstrate the critical role of MsrR-3-MST-MFS in bacterial stress resistance.

Comparison of transcriptional profiles of Treponema pallidum during experimental infection of rabbits and in vitro culture: Highly similar, yet different

“…pallidum (TPANIC_0474) may also affect gene expression, allowing the spirochete to adapt to changing conditions during syphilitic infection, such as increased immune pressure. In addition, TPANIC_0461 is predicted to encode an Xre family [ 56 – 59 ] regulatory protein homolog, and this gene has elevated transcript levels during rabbit infection as compared to in vitro culture ( Table 4 ). Thus it is possible that TPANIC_0461 is capable of altering expression of other genes and aid in adaptation, even in the relatively homeostatic environment of human tissue.…”

Genomics Characterization of an Engineered Corynebacterium glutamicum in Bioreactor Cultivation Under Ionic Liquid Stress

“…Cgl2776 which is a putative XRE family transcriptional regulator MsrR was found to be upregulated from 24 to 65 h. msrR is located downstream of the cmr gene that encodes for a MFS multidrug efflux protein and upstream of Cgl2775/ sseA1 , a sulfurtransferase and Cgl2774. These late-phase upregulated genes have been previously reported to be regulated by MsrR and overexpressed in response to oxidative stress response in C. glutamicum ( Si et al, 2020 ). Genes under the control of DtxR, a master regulator of iron homeostasis at late exponential phase ( Küberl et al, 2020 ), and AmtR, a master regulator of nitrogen metabolism ( Beckers et al, 2005 ) were also upregulated at later time points compared to 6.5 h. The iron homeostasis genes included Cgl0387 (putative membrane protein) and Cgl2035, an ABC-type cobalamin/Fe 3+ -siderophores transporter.…”

Genomics Characterization of an engineered Corynebacterium glutamicum in Bioreactor Cultivation under Ionic Liquid Stress

“…Cgl2776 which is a putative XRE family transcriptional regulator MsrR was found to be upregulated from 24 h to 65 h. msrR is located downstream of the cmr gene that encodes for a MFS multidrug efflux protein and upstream of Cgl2775/sseA1, a sulfurtransferase and Cgl2774. These late-phase upregulated genes have been previously reported to be regulated by MsrR and overexpressed in response to oxidative stress response in C. glutamicum (Si et al, 2020). Genes under the control of DtxR, a master regulator of iron homeostasis at late exponential phase (Küberl et al, 2020), and AmtR, a master regulator of nitrogen metabolism (Beckers et al, 2005) were also upregulated at later time points compared to 6.5 h. The iron homeostasis genes included Cgl0387 (putative membrane protein) and Cgl2035, an ABC-type cobalamin/Fe3+-siderophores Systems Analysis of C. glutamicum 11 transporter.…”