Spatial determinants of quorum signaling in a Pseudomonas aeruginosa infection model

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 18; pp. 4779 - 4784
• Main Authors: Darch, Sophie E., Simoska, Olja, Fitzpatrick, Mignon, Barraza, Juan P., Stevenson, Keith J., Bonnecaze, Roger T., Shear, Jason B., Whiteley, Marvin
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01-05-2018
• Subjects: Aggregates; Bacteria; Biological Sciences; Cell density; Chemical communication; Communications systems; Communities; Cystic fibrosis; Fitness; Heterogeneity; Lung diseases; Opportunist infection; Pseudomonas aeruginosa; Remote sensing; Sensitivity; Signaling; Studies; Three dimensional printing; Viral infections; Pseudomonas aeruginosa; quorum sensing; cystic fibrosis; spatial distribution; aggregate
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1719317115

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.