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Chapter 14 : Interactions of Porphyromonas gingivalis with Human Gingival Epithelium
Category: Genomics and Bioinformatics
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Gingival epithelial cells, the initial lining of gingival mucosa functioning as an important part of the innate immune system, are among the first host cells colonized by Porphyromonas gingivalis. This chapter presents a study which showed that the gingival epithelial cells display a high level of death upon treatment with ATPe and that treatment with purified recombinant Ndk inhibits ATP-mediated host cell plasma membrane permeabilization in a dose-dependent manner. Cytochalasin D, a fungal toxin that disrupts the microfilaments and inhibits actin polymerization, caused significant inhibition of the level of intercellular spread, confirming that the stimulation of actin polymerization is an underlying factor for dissemination of P. gingivalis within the host epithelium. In addition to constituting a physical barrier to the ingress of organisms, epithelial cells can sense and respond to the presence of bacteria following stimulation of pattern recognition receptors (PRRs), resulting in secretion of inflammatory cytokines and differentiation of the epithelial cells. The current challenges include accurate definition of species and identification of the species present at subthresholds. The initiation of inflammation and succession of disease might require a large number of potentially pathogenic populations acting in concert. The current innovative approaches for determining biphasic interaction between host and microbe, particularly identification of mutualistic and/or pathogenic genes and proteins, include suppression subtractive hybridization, comparative genomic analyses by DNA microarrays, and various proteomics technologies.
Sequence comparison of the putative P. gingivalis Ndk (PG1018) with Ndk from different organisms. In the sequences, an asterisk indicates residues implicated in Ndk kinase activity: Y35, N96, and H101. Highly conserved residues are indicated by a dark background, and gaps are indicated by dashes. Accession numbers for the sequences are as follows: Giardia lamblia, XP771399.1; Bacillus sp. strain B14905, ZP01725465.1; Bombyx mori, ABF51506.1; Bos taurus, NP991387.1; Schizosaccharomyces pombe, NP592857.1; Diaphorina citri, ABG81980.1; Pinus pinaster, CAC84493.1; Apis mellifera, XP393351.2; Synechococcus sp. strain CC9311, YP731929.1; Heliobacillus mobilis, AAC84038.1; Canis familiaris, NP001019809.1; Mus domestica, XP001363771.1; Homo sapiens, NP000260.1; and Porphyromonas gingivalis, PG1018 NP905239.1. Sequence alignment of the PG1018 protein from P. gingivalis and representative Ndk proteins from organisms ranging from bacteria to humans was performed using ClustalW. Reprinted from Cellular Microbiology ( 58 ) with permission from the publisher.
Overview of proposed mechanisms of P. gingivalis establishment in gingival epithelium. P. gingivalis infection targets multiple host signaling pathways to ensure its survival in gingival epithelial cells.
Stressed cells release DSs (ATP and adenosine) that can upregulate and downregulate inflammation temporally.