Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT, 06030, USA.
Laboratory of Oral Microbiology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
ISME J. 2021 May;15(5):1490-1504. doi: 10.1038/s41396-020-00865-y. Epub 2020 Dec 28.
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人类相关多微生物群落从健康到疾病的组成变化。然而，驱动这些群落中病原体定植和过度生长的具体过程仍不完全清楚。我们使用体外培养系统和疾病相关的小鼠模型表明，种群大小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共生早期定植者小韦荣球菌提供的一种细胞密度依赖性、促进生长的可溶性分子来克服对内源性信号的需求，而其他测试的共生菌则不产生这种分子。我们的工作表明，多微生物群落中特定早期和晚期定植物种之间细胞密度依赖性可扩散信号的交换驱动微生物演替、病原体定植和疾病发展，这代表了一种针对微生物组操纵以实现健康状态的目标过程。
