Many human infections are polymicrobial in origin, and interactions among community inhabitants shape colonization patterns and pathogenic potential ¹ . Periodontitis, which is the sixth most prevalent infectious disease worldwide ² , ensues from the action of dysbiotic polymicrobial communities ³ . The keystone pathogen Porphyromonas gingivalis and the accessory pathogen Streptococcus gordonii interact to form communities in vitro and exhibit increased fitness in vivo ^3,4 . The mechanistic basis of this polymicrobial synergy, however, has not been fully elucidated. Here we show that streptococcal 4-aminobenzoate/para-amino benzoic acid (pABA) is required for maximal accumulation of P. gingivalis in dual-species communities. Metabolomic and proteomic data showed that exogenous pABA is used for folate biosynthesis, and leads to decreased stress and elevated expression of fimbrial adhesins. Moreover, pABA increased the colonization and survival of P. gingivalis in a murine oral infection model. However, pABA also caused a reduction in virulence in vivo and suppressed extracellular polysaccharide production by P. gingivalis. Collectively, these data reveal a multidimensional aspect to P. gingivalis-S. gordonii interactions and establish pABA as a critical cue produced by a partner species that enhances the fitness of P. gingivalis while diminishing its virulence.

中文翻译：

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代谢串扰调节口腔多种微生物感染期间牙龈卟啉单胞菌的定植和毒力。


许多人类感染都是由多种微生物引起的，社区居民之间的相互作用决定了定植模式和致病潜力¹ 。牙周炎是全球第六大最流行的传染病² ，是由失调的多微生物群落³的作用引起的。主要病原体牙龈卟啉单胞菌和副病原体戈登链球菌相互作用，在体外形成群落，并在体内表现出增强的适应性^3,4 。然而，这种多微生物协同作用的机制基础尚未完全阐明。在这里，我们表明链球菌 4-氨基苯甲酸酯/对氨基苯甲酸 (pABA) 是双物种群落中牙龈卟啉单胞菌最大积累所必需的。代谢组学和蛋白质组学数据表明，外源 pABA 用于叶酸生物合成，并导致应激减少和菌毛粘附素表达升高。此外，pABA 增加了小鼠口腔感染模型中牙龈卟啉单胞菌的定植和存活率。然而，pABA 也会导致体内毒力降低并抑制牙龈卟啉单胞菌胞外多糖的产生。总的来说，这些数据揭示了牙龈卟啉单胞菌-S的多维方面。 gordonii 相互作用，并将 pABA 作为伙伴物种产生的关键线索，增强牙龈卟啉单胞菌的适应性，同时降低其毒力。