Community signalling between Streptococcus gordonii and Porphyromonas gingivalis is controlled by the transcriptional regulator CdhR

Abstract

SummaryInterspecies signalling between Porphyromonas gingivalis and Streptococcus gordonii serves to constrain development of dual species communities. Contact with S. gordonii propagates a tyrosine phosphorylation-dependent signal within P. gingivalis that culminates in reduced transcription of adhesin and signalling genes. Here we demonstrate the involvement of the P. gingivalis orphan LuxR family transcription factor PGN_1373, which we designate CdhR, in this control pathway. Expression of cdhR is elevated following contact with S. gordonii; however, regulation of cdhR did not occur in a mutant lacking the tyrosine phosphatase Ltp1, indicating that CdhR and Ltp1 are components of the same regulon. Contact between S. gordonii and a CdhR mutant resulted in increased transcription of mfa, encoding the subunit of the short fimbriae, along with higher levels of Mfa protein. Expression of luxS, encoding AI-2 synthase, was also increased in the cdhR mutant after contact with S. gordonii. The Mfa adhesive function and AI-2-dependent signalling participate in the formation and development of dual species communities, and consistent with this the cdhR mutant displayed elevated accumulation on a substratum of S. gordonii. Recombinant CdhR protein bound to upstream regulatory regions of both mfa and luxS, indicating that CdhR has a direct effect on gene expression. LuxS was also found to participate in a positive feedback loop that suppresses CdhR expression. Interaction of Mfa fimbriae with S. gordonii is necessary to initiate signalling through CdhR. These results reveal CdhR to be an effector molecule in a negative regulatory network that controls P. gingivalis-S. gordonii heterotypic communities.

The role of kinases and phosphatases in the pathobiology of porphyromonas gingivalis.

“…Previous research from our lab elucidated the role of tyrosine phosphatase, Ltp1, in P. gingivalis-S. gordonii dual species community development [126,135]. We we know from studies of other systems that these types of phosphatases usually have a kinase cognate pair as has been reported in E. coli as well as S. pneumoniae.…”

“…Once activated, CdhR negatively regulates expression of the mfa1 gene encoding the Mfa1 co-adhesin [126]. Deletion of the ltp1 gene, or loss of tyrosine phosphatase activity through expression of a catalytically inactive mutant, increases the level of P. gingivalis accumulation with S. gordonii [135].…”

“…gingivalis with S. gordonii [126]), we predicted that this Ptk1 kinase would yield an opposite effect and thereby promote P. gingivalis-S. gordonii community formation. The P. gingivalis strains, 33277 (WT), Δptk1, and Δptk1+pptk1 complemented mutant, were all labeled with FITC (green).…”

“…Transcription of ltp1 is increased following contact with S. gordonii [125], and Ltp1 is a component of a signaling pathway that converges on the LuxR family transcriptional regulator CdhR [126]. The expression of the P. gingivalis…”

“…gordonii by upregulating and activating the transcription factor CdhR (Community Development and Hemin Regulator), an orphan LuxR family transcriptional regulator [126,135]. Once activated, CdhR negatively regulates expression of the mfa1 gene encoding the Mfa1 co-adhesin [126].…”