Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizer Veillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state.

最近的研究详细描述了与人类相关的多种微生物群落的组成从健康到疾病的转变。然而，驱动这些社区内病原体定植和过度生长的具体过程仍未完全了解。我们使用体外培养系统和与疾病相关的小鼠模型来显示种群大小，它决定了内源性可扩散小分子的可用性，限制了人类口腔病原体牙龈卟啉单胞菌的生长、定植和体内毒力。这种细菌病原体通过利用由共生的早期定殖者 Veillonella parvula提供的细胞密度依赖性、促进生长的可溶性分子，克服了对内源性线索的需求，但不是由其他经过测试的共生体产生的。我们的工作表明，在多微生物群落中特定的早期和晚期定殖物种之间交换依赖于细胞密度的可扩散线索推动了微生物演替、病原体定殖和疾病发展，代表了将微生物组操纵到健康状态的目标过程。