Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
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Query: UMLS:C0031099 (
periodontitis
)
12,489
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
Porphyromonas gingivalis
, 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
php1
gene is located immediately downstream of the gene encoding the bacterial tyrosine (BY) kinase Ptk1, which was a substrate for Php1
in vitro
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
P. gingivalis
exopolysaccharide production and for community development with the antecedent oral biofilm constituent
Streptococcus gordonii
under nutrient-depleted conditions. In contrast, the absence of Php1 had no effect on the ability of
P. gingivalis
to form monospecies biofilms.
In vitro
, Php1 enzymatic activity was resistant to the effects of the streptococcal secreted metabolites pABA and H
2
O
2
, 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
P. gingivalis
nonvirulent in an animal model of periodontal disease. Collectively, these results demonstrate that
P. gingivalis
possesses active PHP and LMW tyrosine phosphatases, a unique configuration in Gram-negatives which may allow
P. gingivalis
to maintain phosphorylation/dephosphorylation homeostasis in multispecies communities. Moreover, Php1 contributes to the pathogenic potential of the organism.
IMPORTANCE
Periodontal diseases are among the most common infections of humans and are also associated with systemic inflammatory conditions. Colonization and pathogenicity of
P. gingivalis
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
P. gingivalis
community development with other oral bacteria, and in the absence of Php1 activity
P. gingivalis
was unable to cause disease in a mouse model of
periodontitis
. This work provides significant insights into the protein tyrosine (de)phosphorylation network in
P. gingivalis
, its adaptation to heterotypic communities, and its contribution to colonization and virulence.
...
PMID:Porphyromonas gingivalis Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity. 3155 34
