Abstract
Our understanding of how the oral anaerobe Porphyromonas gingivalis can persist below the gum line, induce ecological changes, and promote polymicrobial infections remains limited. P. gingivalis has long been described as a highly proteolytic and asaccharolytic pathogen that utilizes protein substrates as the main source for energy production and proliferation. Here, we report that P. gingivalis displays a metabolic plasticity that enables the exploitation of non-proteinaceous substrates, specifically the monocarboxylates pyruvate and lactate, as well as human serum components, for colonization and biofilm formation. We show that anabolism of carbohydrates from pyruvate is powered by catabolism of amino acids. Concomitantly, the expression of fimbrial adhesion is upregulated, leading to the enhancement of biofilm formation, stimulation of multispecies biofilm development, and increase of colonization and invasion of the primary gingival epithelial cells by P. gingivalis. These studies provide the first glimpse into the metabolic plasticity of P. gingivalis and its adaptation to the nutritional condition of the host niche. Our findings support the model that in response to specific nutritional parameters, P. gingivalis has the potential to promote host colonization and development of a pathogenic community.
Highlights
An orchestrated series of dysbiotic polymicrobial interactions can promote the colonization of a pathogenic microbial community below the gum line, leading to periodontitis, an infection-driven inflammatory disease of the periodontal tissues and alveolar bone, imposing adverse systemic effects on human health[1,2,3,4,5]
P. gingivalis can persist in the subgingival ecosystem adjacent to the epithelium, even in the absence of periodontitis in an otherwise healthy individual[8,9,10,11]; it is speculated that an unknown ecophysiological condition allows P. gingivalis strains to transition toward a pathogenic state, and to produce an array of pathogenicity factors, including the type IX secretion system (T9SS), proteases, and fimbrial adhesions, that promote bacterial proliferation, persistence, and invasion[6,12,13]
To a much less degree, P. intermedia, S. intermedius, and F. alocis could positively respond to pyruvate addition. These findings indicated that P. gingivalis has evolved with a yet unreported metabolic plasticity that enables efficient utilization of host-driven non-proteinaceous substrates, as well as serum components toward enhancing surface colonization and biofilm development
Summary
An orchestrated series of dysbiotic polymicrobial interactions can promote the colonization of a pathogenic microbial community below the gum line, leading to periodontitis, an infection-driven inflammatory disease of the periodontal tissues and alveolar bone, imposing adverse systemic effects on human health[1,2,3,4,5]. Consistent with the biofilm data showing that lactate has an inhibitive effect on biofilm formation, the addition of lactate to the BSA-based medium could downregulate the expression of all targeted genes, including fimA expression (by 2.3 times), when compared with the BSA-only medium (Fig. 3a, c) Overall, these findings revealed that specific pathogenicity factors are differentially expressed in response to the availability of key biologically relevant substrates; the expression of fimA is greatly affected by the availability of pyruvate and lactate. Given that pyruvate plays a central role in several metabolic pathways in all organisms, and our findings showed that it greatly enhances fimbria-mediated attachment and biofilm formation, we aimed at revealing the impact of concomitant utilization of pyruvate and serum components on metabolic status of P. gingivalis during biofilm growth To this end, we performed a global metabolomic analysis on the metabolome of the biofilm cells grown in HSA or human serum with and without pyruvate addition. These findings support our notion that exogenous pyruvate is tied to the metabolism of serum components toward the enhancement of the PPP and biosynthetic processes that are required during the biofilm development (see “Discussion” for the proposed model)
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