Phosphorylation of major Porphyromonas gingivalis virulence factors is crucial for their processing and secretion.


Journal

Molecular oral microbiology
ISSN: 2041-1014
Titre abrégé: Mol Oral Microbiol
Pays: Denmark
ID NLM: 101524770

Informations de publication

Date de publication:
12 2021
Historique:
revised: 17 09 2021
received: 16 08 2021
accepted: 20 09 2021
pubmed: 28 9 2021
medline: 11 11 2021
entrez: 27 9 2021
Statut: ppublish

Résumé

The main etiological agent of periodontitis is the anaerobic bacterium Porphyromonas gingivalis. Virulence of this pathogen is controlled by various mechanisms and executed by major virulence factors including the gingipain proteases, peptidylarginine deiminase (PPAD), and RagB, an outer membrane macromolecular transport component. Although the structures and functions of these proteins are well characterized, little is known about their posttranslational maturation. Here, we determined the phosphoproteome of P. gingivalis in which phosphorylated tyrosine residues constitute over 80% of all phosphoresidues. Multiple phosphotyrosines were found in gingipains, PPAD, and RagB. Although mutation of phosphorylated residues in PPAD and RagB had no effect on secretion or activity, site-directed mutagenesis showed that phosphorylation in hemagglutinin/adhesin domains of RgpA and Kgp, and in the catalytic domain of RgpB, had a strong influence on secretion, processing, and enzymatic activity. Moreover, preventing phosphorylation of one gingipain influenced the others, suggesting multiple phosphorylation-dependent pathways of gingipain maturation in P. gingivalis. Various candidate kinases including Ptk1 BY kinase and ubiquitous bacterial kinase 1 (UbK1) may be involved, but their contribution to gingipain processing and activation remains to be confirmed.

Identifiants

pubmed: 34569151
doi: 10.1111/omi.12354
pmc: PMC10148667
mid: NIHMS1891064
doi:

Substances chimiques

Adhesins, Bacterial 0
Hemagglutinins 0
RNA, Ribosomal, 16S 0
Virulence Factors 0
Cysteine Endopeptidases EC 3.4.22.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

316-326

Subventions

Organisme : NIDCR NIH HHS
ID : R00 DE028346
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE011111
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE012505
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE023193
Pays : United States

Informations de copyright

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Auteurs

Zuzanna Nowakowska (Z)

Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

Mariusz Madej (M)

Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

Sylwia Grad (S)

Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.

Tiansong Wang (T)

Department of Chemical Engineering, University of Washington, Seattle, Washington, USA.

Murray Hackett (M)

Department of Chemical Engineering, University of Washington, Seattle, Washington, USA.

Daniel P Miller (DP)

Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.

Richard J Lamont (RJ)

Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA.

Jan Potempa (J)

Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Krakow, Poland.
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA.

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Classifications MeSH