Abstract
BackgroundPolyphosphate (polyP) has bactericidal activity against a gram-negative periodontopathogen Porphyromonas gingivalis, a black-pigmented gram-negative anaerobic rod. However, current knowledge about the mode of action of polyP against P. gingivalis is incomplete. To elucidate the mechanisms of antibacterial action of polyP against P. gingivalis, we performed the full-genome gene expression microarrays, and gene ontology (GO) and protein-protein interaction network analysis of differentially expressed genes (DEGs).ResultsWe successfully identified 349 up-regulated genes and 357 down-regulated genes (>1.5-fold, P < 0.05) in P. gingivalis W83 treated with polyP75 (sodium polyphosphate, Nan+2PnO3n+1; n = 75). Real-time PCR confirmed the up- and down-regulation of some selected genes. GO analysis of the DEGs identified distinct biological themes. Using 202 DEGs belonging to the biological themes, we generated the protein-protein interaction network based on a database of known and predicted protein interactions. The network analysis identified biological meaningful clusters related to hemin acquisition, energy metabolism, cell envelope and cell division, ribosomal proteins, and transposon function.ConclusionspolyP probably exerts its antibacterial effect through inhibition of hemin acquisition by the bacterium, resulting in severe perturbation of energy metabolism, cell envelope biosynthesis and cell division, and elevated transposition. Further studies will be needed to elucidate the exact mechanism by which polyP induces up-regulation of the genes related to ribosomal proteins. Our results will shed new light on the study of the antibacterial mechanism of polyP against other related bacteria belonging to the black-pigmented Bacteroides species.
Highlights
Polyphosphate has bactericidal activity against a gram-negative periodontopathogen Porphyromonas gingivalis, a black-pigmented gram-negative anaerobic rod
Inorganic polyphosphate is a chain of few or many hundreds of phosphate (Pi) residues linked by high-energy phosphoanhydride [1]. polyP has attracted considerable attention as a GRAS food additive by FDA with antimicrobial properties that can prevent spoilage of food [2,3]. polyP inhibits the growth of various gram-positive bacteria such as Staphylococcus aureus [4,5,6,7,8], Listeria monocytogenes [8,9], Sarcina lutea [7], Bacillus cereus [10], and mutans
Down-regulated genes were related to iron/hemin acquisition, energy metabolism and electron carriers, and cell envelope and cell division
Summary
Polyphosphate (polyP) has bactericidal activity against a gram-negative periodontopathogen Porphyromonas gingivalis, a black-pigmented gram-negative anaerobic rod. To elucidate the mechanisms of antibacterial action of polyP against P. gingivalis, we performed the full-genome gene expression microarrays, and gene ontology (GO) and protein-protein interaction network analysis of differentially expressed genes (DEGs). In our previous study [16], polyP (Nan+2PnO3n+1; n = the number of phosphorus atoms in the chain) with different linear phosphorus (Pi) chain lengths (3 to 75) demonstrated to have antibacterial activity against Porphyromonas gingivalis, a black pigmented, gram-negative periodontopathogen. PolyP showed antibacterial activity against other black-pigmented, gram-negative oral anaerobes such as Prevotella intermedia and Porphyromonas endodontalis [17,18]. We performed the full-genome gene expression microarrays of P. gingivalis, and gene ontology (GO) and protein-protein interaction network analysis of the differentially expressed genes were performed for elucidating the mechanism of antibacterial action of polyP
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