A Porphyromonas gingivalis tyrosine phosphatase is a multifunctional regulator of virulence attributes

Abstract

Low Molecular Weight Tyrosine Phosphatases (LMWTP) are widespread in prokaryotes; however, understanding of the signaling cascades controlled by these enzymes is still emerging. P. gingivalis, an opportunistic oral pathogen, expresses a LMWTP, Ltp1, that is differentially regulated in biofilm communities. Here we characterize the enzymatic activity of Ltp1 and, through the use of mutants that lack Ltp1 or expresses catalytically defective Ltp1, show that tyrosine phosphatase activity constrains both monospecies biofilm development and community development with the antecedent oral biofilm constituent S. gordonii. Exopolysaccharide production is downregulated by Ltp1 through transcriptional regulation of multiple genes involved in biosynthesis and transport. Furthermore, Ltp1 regulates transcriptional activity of luxS and thus impacts AI-2 dependent signaling in biofilm communities. In the absence of Ltp1 transcription across the hmu hemin uptake locus is reduced, and consequently uptake of hemin is impaired in the Ltp1 mutant. The gingipain proteinases Kgp and RgpA/B remain phosphorylated in the Ltp1 mutant. Phosphorylated Rgps are poorly secreted, whereas cell surface activity of phosphorylated Kgp is enhanced. By controlling the activity of several virulence-associated properties, Ltp1 may restrain the pathogenic potential of P. gingivalis and maintain a commensal interaction with the host.

The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis

“…In addition, regulatory mechanisms controlling expression of iron acquisition genes have been identified, including the transcriptional activator encoded by PG1237, which has been shown to control expression of the hmu locus (Wu et al, 2009). It has also been shown that haemin uptake is significantly reduced in the absence of Ltp1 (PG1641), a tyrosine phosphatase with regulatory function (Maeda et al, 2008). There are also data indicating that expression of luxS (PG0498) is linked to changes in expression of iron acquisition genes (Chung et al, 2001;James et al, 2006).…”

Two-component signal transduction systems in oral bacteria

“…The third signal transduction system could be defined as a variant of the TCS in the sense that the activation of the RR by the sensor protein involves multiple steps of transference of the phosphate group to intermediary proteins [17]. Additional phosphate signalling activities with similarities to eukaryotic pathways have been detected in prokaryotes including P. gingivalis [18,19]. …”

Porphyromonas gingivalis infection in gestational diabetes mellitus and survival in tobacco smokers.

“…PGN_1200 encodes a protein involved in DNA replication and repair. PGN_0491 (Ltp1) encodes phosphotyrosine protein phosphatase probable phosphotyrosine protein phosphatase, which regulates the expression of luxS and exopolysaccharide synthesis, which play a significant role in biofilm formation [355]. PGN_0287 (mfa1), encodes minor fimbrium subunit mfa1.…”