Abstract
Porphyromonas gingivalis is an oral human pathogen. The bacterium destroys dental tissue and is a serious health problem worldwide. Experimental data and bioinformatic analysis revealed that the pathogen produces three types of lipopolysaccharides (LPS): normal (O-type), anionic (A-type), and capsular (K-type). The enzymes involved in the production of all three types of lipopolysaccharide have been largely identified for the first two and partially for the third type. In the current work, we use bioinformatics tools to predict biosynthetic pathways for the production of the normal (O-type) lipopolysaccharide in the W50 strain Porphyromonas gingivalis and compare the pathway with other putative pathways in fully sequenced and completed genomes of other pathogenic strains. Selected enzymes from the pathway have been modeled and putative structures are presented. The pathway for the A-type antigen could not be predicted at this time due to two mutually exclusive structures proposed in the literature. The pathway for K-type antigen biosynthesis could not be predicted either due to the lack of structural data for the antigen. However, pathways for the synthesis of lipid A, its core components, and the O-type antigen ligase reaction have been proposed based on a combination of experimental data and bioinformatic analyses. The predicted pathways are compared with known pathways in other systems and discussed. It is the first report in the literature showing, in detail, predicted pathways for the synthesis of selected LPS components for the model W50 strain of P. gingivalis.
Highlights
Porphyromonas gingivalis is a common human pathogen of the oral cavity
The analysis identified the genes involved in the biosynthesis of the O-type antigen and other lipid core components needed for LPS biosynthesis
Pathway/Genome Databases (PGDBs) are generated computationally by comparison of the genome annotation to manually curated data in the MetaCyc database. This type of database integrates the genomic data of an organism with its predicted metabolic network, including full reaction data, Enzyme Commission (EC) numbers [37], and metabolic pathways
Summary
Porphyromonas gingivalis is a common human pathogen of the oral cavity. The bacterium, which is an obligate anaerobe, is responsible for the destruction of dental tissue, leading to periodontitis [1]. Systems biology analysis of the metabolic network has identified conserved pathways used in lipopolysaccharide (LPS) synthesis by P. gingivalis [2]. Research by other groups identified a type IX secretion system (T9SS) responsible for gingipain secretion [18,19]. Blocking this system could be an indirect strategy for the prevention of periodontitis caused by P. gingivalis [20]. The analysis identified the genes involved in the biosynthesis of the O-type antigen and other lipid core components needed for LPS biosynthesis. The work presented here is the first in the Pathogens 2021, 10, 374 literature reporting a detailed assignment of genes and reactions for the P. gingivalis O-type antigen biosynthetic pathway and its core components. The implications are discussed for general genome-wide metabolic pathway prediction
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