The Novel Streptococcal Transcriptional Regulator XtgS Negatively Regulates Bacterial Virulence and Directly Represses PseP Transcription

Abstract

Streptococcus agalactiae (GBS) has received continuous attention for its involvement in invasive infections and its broad host range. Transcriptional regulators have an important impact on bacterial adaptation to various environments. Researches on the transcriptional regulators will provide new ideas to illuminate GBS pathogenesis. In this study, we identified a novel XRE family transcriptional regulator encoded on the GBS genome, designated XtgS. Our data demonstrated that XtgS inactivation significantly increases bacterial survival in host blood and animal challenge test, suggesting that it is a negative regulator of GBS pathogenicity. Further transcriptomic analysis and qRT-PCR mainly indicated that XtgS significantly repressed its upstream gene PseP transcription. Based on electrophoretic mobility shift and lacZ fusion assays, we found an XtgS homodimer directly binds a palindromic sequence in the PseP promotor region. Meanwhile, the PseP and XtgS assembly naturally co-exists in diverse Streptococcus genomes and has a strong association with ST, serotype diversification and host adaptation of GBS. Therefore, this study reveals that XtgS functions as a transcriptional regulators that negatively affects GBS virulence, directly repressed the PseP expression and provides new insights into the relationships between transcriptional regulator and genome evolution.

Screening for Virulence-Related Genes via a Transposon Mutant Library of Streptococcus suis Serotype 2 Using a Galleria mellonella Larvae Infection Model

“…In Staphylococcus aureus , the XRE family transcriptional regulator XdrA was reported to control the expression of the virulence gene spa [ 43 ]. In group B streptococcus , XtgS was demonstrated to negatively regulate its virulence by directly repressing pseP transcription [ 47 ]. In our study, deletion of hxtR seemed to interfere with the expression of its upstream gene, which is a hypothetical gene.…”

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.…”

XRE Family Transcriptional Regulator XtrSs Modulates Streptococcus Suis Fitness of Hydrogen Peroxide Stress

“…The XRE family transcriptional regulators contain the HTH domain that can bind to the promoter of the target genes and modulate their transcription. We previously characterized an XRE family transcriptional regulator XtgS that negatively regulates virulence in Streptococcus agalactiae (Liu et al 2020).…”

“…DNA probes were obtained by PCR amplification using specific primers (Table S2) and purified using a gel extraction kit (Vazyme, China). The EMSA reaction system was 20 μ L: 100 ng DNA fragment was mixed with more and more purified recombinant protein rXtrSs dimer (0 to 250 ng) in the binding buffer (10 mM Tris, 20 mM KCl, 1 mM EDTA, 5 mM MgCl2, 1 mM dithiothreitol [DTT], 0.05% and 5% glycerol [vol/vol]) (Guyet et al 2013;Liu et al 2020). The EMSA mixtures were incubated at 37°C for 30 min, then loaded onto a 6% polyacrylamide gel in 0.5× TBE buffer (44.5 mM Tris base, 44.5 mM boric acid, 1 mM EDTA, pH 7.4) and electrophoresed at 200 V for 45 min.…”