<i>Porphyromonas gingivalis</i> and <i>Treponema denticola</i> Exhibit Metabolic Symbioses

<div><p><i>Porphyromonas gingivalis</i> and <i>Treponema denticola</i> are strongly associated with chronic periodontitis. These bacteria have been co-localized in subgingival plaque and demonstrated to exhibit symbiosis in growth <i>in vitro</i> and synergistic virulence upon co-infection in animal models of disease. Here we show that during continuous co-culture a <i>P. gingivalis:T. denticola</i> cell ratio of 6∶1 was maintained with a respective increase of 54% and 30% in cell numbers when compared with mono-culture. Co-culture caused significant changes in global gene expression in both species with altered expression of 184 <i>T. denticola</i> and 134 <i>P. gingivalis</i> genes. <i>P. gingivalis</i> genes encoding a predicted thiamine biosynthesis pathway were up-regulated whilst genes involved in fatty acid biosynthesis were down-regulated. <i>T. denticola</i> genes encoding virulence factors including dentilisin and glycine catabolic pathways were significantly up-regulated during co-culture. Metabolic labeling using ¹³C-glycine showed that <i>T. denticola</i> rapidly metabolized this amino acid resulting in the production of acetate and lactate. <i>P. gingivalis</i> may be an important source of free glycine for <i>T. denticola</i> as mono-cultures of <i>P. gingivalis</i> and <i>T. denticola</i> were found to produce and consume free glycine, respectively; free glycine production by <i>P. gingivalis</i> was stimulated by <i>T. denticola</i> conditioned medium and glycine supplementation of <i>T. denticola</i> medium increased final cell density 1.7-fold. Collectively these data show <i>P. gingivalis</i> and <i>T. denticola</i> respond metabolically to the presence of each other with <i>T. denticola</i> displaying responses that help explain enhanced virulence of co-infections.</p>