Gingimaps: Protein Localization in the Oral Pathogen Porphyromonas gingivalis

Abstract

Porphyromonas gingivalis is an oral pathogen involved in the widespread disease periodontitis. In recent years, however, this bacterium has been implicated in the etiology of another common disorder, the autoimmune disease rheumatoid arthritis. Periodontitis and rheumatoid arthritis were known to correlate for decades, but only recently a possible molecular connection underlying this association has been unveiled. P. gingivalis possesses an enzyme that citrullinates certain host proteins and, potentially, elicits autoimmune antibodies against such citrullinated proteins. These autoantibodies are highly specific for rheumatoid arthritis and have been purported both as a symptom and a potential cause of the disease. The citrullinating enzyme and other major virulence factors of P. gingivalis, including some that were implicated in the etiology of rheumatoid arthritis, are targeted to the host tissue as secreted or outer-membrane-bound proteins. These targeting events play pivotal roles in the interactions between the pathogen and its human host. Accordingly, the overall protein sorting and secretion events in P. gingivalis are of prime relevance for understanding its full disease-causing potential and for developing preventive and therapeutic approaches. The aim of this review is therefore to offer a comprehensive overview of the subcellular and extracellular localization of all proteins in three reference strains and four clinical isolates of P. gingivalis, as well as the mechanisms employed to reach these destinations.

Keywords: OMV; P. gingivalis; PPAD; Porphyromonas gingivalis; protein sorting; proteome.

FIG 1

P. gingivalis: electron micrographs of P. gingivalis type strain W83 (A) and the clinical strains 505700 (B), 512915 (C), 505759 (D), and MDS33 (E and F). Note the capture of OMV formation in panels A, B, C, and E (marked by white arrows).

FIG 2

Protein sorting mechanisms in P. gingivalis. An overview diagram shows the cellular architecture and protein transport systems that occur in P. gingivalis. The indicated protein transport systems were identified by domain searches for major components of known transport systems previously observed in Gram-negative bacteria. The Lol, Bam, T4SS, and T5SS systems for which only a limited number of known potential components were identified in P. gingivalis are indicated in parentheses. SP, signal peptide.

FIG 3

OMVs are the “satellite compartments” of P. gingivalis. A transmission electron micrograph shows the purified outer membrane vesicles of P. gingivalis type strain W83.

FIG 4

Bioinformatics pipeline to unravel protein sorting events in P. gingivalis. The flowchart depicts the different steps used to assess the subcellular localization of proteins in the analyzed P. gingivalis strains.

FIG 5

Biological pathways represented in the P. gingivalis core exoproteome. A REVIGO tree map depicts the outcome of a GO term analysis of cellular pathways involving the proteins predicted to define the core exoproteome of the P. gingivalis strains under examination.

FIG 6

Biological pathways represented by the P. gingivalis variable exoproteome. REVIGO tree maps represent the outcomes of GO term analyses of the cellular pathways in which variable exoproteomes of different P. gingivalis strains are involved. (A) MDS140; (B) W83; (C) TDC60, MDS33, and 512915; (D) ATCC 33277 and 20655.

FIG 7

Overview of subcellular localization of core and variant P. gingivalis proteins. The numbers of proteins residing at a particular subcellular location, or extracellularly, are indicated for the core proteome and the variable proteome of each examined P. gingivalis strain. Specifically, these include strains ATCC 33277, W83, TDC60, MDS33, MDS140, 512915, and 20655. The numbers of cytoplasmic proteins are indicated in blue, IM lipoproteins in red, IM proteins in black, periplasmic proteins in green, OM lipoproteins in orange, OM proteins in yellow, PorSS secreted proteins in gray, and ECP-secreted proteins in cyan.