Porphyromonas gingivalis Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity

• Published in: mBio 2019-09, Vol.10 (5)
• Main Authors: Jung, Young-Jung, Miller, Daniel P, Perpich, John D, Fitzsimonds, Zackary R, Shen, Daonan, Ohshima, Jun, Lamont, Richard J
• Format: Article
• Language: English
• Subjects: Bacterial Load - drug effects; Bacterial Physiological Phenomena - drug effects; Host-Microbe Biology; Humans; microbial communities; periodontitis; Porphyromonas gingivalis - physiology; Protein Tyrosine Phosphatases - metabolism; tyrosine phosphatase; Virulence - physiology
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mbio.02004-19

Protein-tyrosine phosphorylation in bacteria plays a significant role in multiple cellular functions, including those related to community development and virulence. Metal-dependent protein tyrosine phosphatases that belong to the polymerase and histindinol phosphatase (PHP) family are widespread in Gram-positive bacteria. Here, we show that , a Gram-negative periodontal pathogen, expresses a PHP protein, Php1, with divalent metal ion-dependent tyrosine phosphatase activity. Php1 tyrosine phosphatase activity was attenuated by mutation of conserved histidine residues that are important for the coordination of metal ions and by mutation of a conserved arginine residue, a key residue for catalysis in other bacterial PHPs. The gene is located immediately downstream of the gene encoding the bacterial tyrosine (BY) kinase Ptk1, which was a substrate for Php1 Php1 rapidly caused the conversion of Ptk1 to a state of low tyrosine phosphorylation in the absence of discernible intermediate phosphoforms. Active Php1 was required for exopolysaccharide production and for community development with the antecedent oral biofilm constituent under nutrient-depleted conditions. In contrast, the absence of Php1 had no effect on the ability of to form monospecies biofilms. , Php1 enzymatic activity was resistant to the effects of the streptococcal secreted metabolites pABA and H O , which inhibited Ltp1, an enzyme in the low-molecular-weight (LMW) phosphotyrosine phosphatase family. Ptk1 reciprocally phosphorylated Php1 on tyrosine residues 159 and 161, which independently impacted phosphatase activity. Loss of Php1 rendered nonvirulent in an animal model of periodontal disease. Collectively, these results demonstrate that possesses active PHP and LMW tyrosine phosphatases, a unique configuration in Gram-negatives which may allow to maintain phosphorylation/dephosphorylation homeostasis in multispecies communities. Moreover, Php1 contributes to the pathogenic potential of the organism. Periodontal diseases are among the most common infections of humans and are also associated with systemic inflammatory conditions. Colonization and pathogenicity of are regulated by signal transduction pathways based on protein tyrosine phosphorylation and dephosphorylation. Here, we identify and characterize a novel component of the tyrosine (de)phosphorylation axis: a polymerase and histindinol phosphatase (PHP) family enzyme. This tyrosine phosphatase, designated Php1, was required for commun