A PorX/PorY and sP Feedforward Regulatory Loop Controls Gene Expression Essential for Porphyromonas gingivalis Virulence

Chizhou Jiang, Dezhi Yang, Tangsiyuan Hua, Zichun Hua, Wei Kong, Yixin Shia

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6 Scopus citations


The PorX/PorY two-component system in the periodontal pathogen Porphyromonas gingivalis controls the expression of the por genes, encoding a type IX secretion system, and the sigP gene, encoding sigma factor sP. Previous results implied that PorX/PorY and sP formed a regulatory cascade because the PorX/PorY-activated sP enhanced the por genes, including porT, via binding to their promoters. We recently showed that PorX also binds to the por promoters, thus suggesting that an alternative mechanism is required for the PorX/PorY- and sP-governed expression. Here, our in vitro assays show the PorX response regulator binds to the sigP promoter at a sequence shared with the porT promoter and enhances its transcription, mediated by a reconstituted P. gingivalis RNA polymerase holoenzyme. Merely producing sP in trans fails to reverse the porT transcription in a porX mutant, which further argues against the action of the proposed regulatory cascade. An in vitro transcription assay using a reconstituted RNA polymerase-sP holoenzyme verifies the direct role of PorX in porT transcription, since transcription is enhanced by a pure PorX protein. Accordingly, we propose that the PorX/PorY system coordinates with sP to construct a coherent regulatory mechanism, known as the feedforward loop. Specifically, PorX will not only bind to the sigP promoter to stimulate the expression of sP, but also bind to the porT promoter to facilitate the RNA polymerase-sP-dependent transcription. Importantly, mutations at the porX and sigP genes attenuate bacterial virulence in a mouse model, demonstrating that this regulatory mechanism is essential for P. gingivalis pathogenesis. IMPORTANCE The anaerobic bacterium Porphyromonas gingivalis is not only the major etiologic agent for chronic periodontitis, but also prevalent in some common noncommunicable diseases such as cardiovascular disease, Alzheimer's disease, and rheumatoid arthritis. We present genetic, biochemical, and biological results to demonstrate that the PorX/PorY two-component system and sigma factor sP build a specific regulatory network to coordinately control transcription of the genes encoding the type IX secretion system, and perhaps also other virulence factors. Results in this study verify that the response regulator PorX stimulates the expression of the genes encoding both sP and the type IX secretion system by binding to their promoters. This study also provides evidence that sP, like the PorX/PorY system, contributes to P. gingivalis virulence in a mouse model.

Original languageEnglish (US)
Article numbere00428-21
Issue number3
StatePublished - May 2021


  • Extracytoplasmic function sigma factor P
  • Feedforward loop
  • In vitro transcription
  • PorX/PorY
  • Porphyromonas gingivalis
  • Transcription regulation
  • Two-component system
  • Type IX secretion system
  • Virulence factors

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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