<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity

ABSTRACT 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 wide...

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Autores principales:	Young-Jung Jung, Daniel P. Miller, John D. Perpich, Zackary R. Fitzsimonds, Daonan Shen, Jun Ohshima, Richard J. Lamont
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	microbial communities periodontitis tyrosine phosphatase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/13ff759c76fe4cda8167ba8cbd6a5c60
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spelling	oai:doaj.org-article:13ff759c76fe4cda8167ba8cbd6a5c602021-11-15T15:59:41Z<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity10.1128/mBio.02004-192150-7511https://doaj.org/article/13ff759c76fe4cda8167ba8cbd6a5c602019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02004-19https://doaj.org/toc/2150-7511ABSTRACT 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 H2O2, 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.Young-Jung JungDaniel P. MillerJohn D. PerpichZackary R. FitzsimondsDaonan ShenJun OhshimaRichard J. LamontAmerican Society for Microbiologyarticlemicrobial communitiesperiodontitistyrosine phosphataseMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	microbial communities periodontitis tyrosine phosphatase Microbiology QR1-502
spellingShingle	microbial communities periodontitis tyrosine phosphatase Microbiology QR1-502 Young-Jung Jung Daniel P. Miller John D. Perpich Zackary R. Fitzsimonds Daonan Shen Jun Ohshima Richard J. Lamont <named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity
description	ABSTRACT 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 H2O2, 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.
format	article
author	Young-Jung Jung Daniel P. Miller John D. Perpich Zackary R. Fitzsimonds Daonan Shen Jun Ohshima Richard J. Lamont
author_facet	Young-Jung Jung Daniel P. Miller John D. Perpich Zackary R. Fitzsimonds Daonan Shen Jun Ohshima Richard J. Lamont
author_sort	Young-Jung Jung
title	<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity
title_short	<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity
title_full	<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity
title_fullStr	<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity
title_full_unstemmed	<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity
title_sort	<named-content content-type="genus-species">porphyromonas gingivalis</named-content> tyrosine phosphatase php1 promotes community development and pathogenicity
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/13ff759c76fe4cda8167ba8cbd6a5c60
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<named-content content-type="genus-species">Porphyromonas gingivalis</named-content> Tyrosine Phosphatase Php1 Promotes Community Development and Pathogenicity

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