期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：18
页码：4779-4784
DOI：10.1073/pnas.1719317115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Quorum sensing (QS) is a bacterial communication system that involves production and sensing of extracellular signals. In laboratory models, QS allows bacteria to monitor and respond to their own cell density and is critical for fitness. However, how QS proceeds in natural, spatially structured bacterial communities is not well understood, which significantly hampers our understanding of the emergent properties of natural communities. To address this gap, we assessed QS signaling in the opportunistic pathogen Pseudomonas aeruginosa in a cystic fibrosis (CF) lung infection model that recapitulates the biogeographical aspects of the natural human infection. In this model, P. aeruginosa grows as spatially organized, highly dense aggregates similar to those observed in the human CF lung. By combining this natural aggregate system with a micro-3D–printing platform that allows for confinement and precise spatial positioning of P. aeruginosa aggregates, we assessed the impact of aggregate size and spatial positioning on both intra- and interaggregate signaling. We discovered that aggregates containing ∼2,000 signal-producing P. aeruginosa were unable to signal neighboring aggregates, while those containing ≥5,000 cells signaled aggregates as far away as 176 µm. Not all aggregates within this “calling distance” responded, indicating that aggregates have differential sensitivities to signal. Overexpression of the signal receptor increased aggregate sensitivity to signal, suggesting that the ability of aggregates to respond is defined in part by receptor levels. These studies provide quantitative benchmark data for the impact of spatial arrangement and phenotypic heterogeneity on P. aeruginosa signaling in vivo.
关键词：Pseudomonas aeruginosa ; aggregate ; quorum sensing ; cystic fibrosis ; spatial distribution
