Porphyromonas gingivalis Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity

Area of Science:

• Microbiology and Molecular Biology
• Bacterial Pathogenesis
• Signal Transduction

Background:

• Protein-tyrosine phosphorylation is vital for bacterial cellular functions, including community development and virulence.
• Metal-dependent protein tyrosine phosphatases of the polymerase and histidino l phosphatase (PHP) family are common in Gram-positive bacteria.

Purpose of the Study:

• To identify and characterize a PHP family protein tyrosine phosphatase (Php1) in the Gram-negative periodontal pathogen Porphyromonas gingivalis.
• To elucidate the role of Php1 in P. gingivalis physiology, community development, and virulence.

Main Methods:

• Biochemical characterization of Php1's tyrosine phosphatase activity, including metal ion dependency and effects of mutations.
• Identification of Ptk1 (bacterial tyrosine kinase) as a substrate for Php1.
• Assessment of Php1's role in P. gingivalis exopolysaccharide production, monospecies, and multispecies biofilm formation.
• Evaluation of P. gingivalis virulence in an animal model of periodontal disease following Php1 deletion.

Main Results:

• P. gingivalis expresses Php1, a PHP family tyrosine phosphatase with divalent metal ion-dependent activity.
• Php1 dephosphorylates Ptk1 and is essential for exopolysaccharide production and P. gingivalis community development with Streptococcus gordonii.
• Loss of Php1 renders P. gingivalis nonvirulent in a mouse model of periodontal disease.

Conclusions:

• P. gingivalis possesses both PHP and LMW tyrosine phosphatases, a unique configuration that may aid in maintaining phosphorylation homeostasis in multispecies communities.
• Php1 plays a critical role in P. gingivalis virulence and adaptation to complex oral environments.
• Php1 is a significant contributor to the pathogenic potential of P. gingivalis.