Distal modulation of bacterial cell–cell signalling in a synthetic ecosystem using partitioned microfluidics

Introduction When culturing bacteria in artificial microhabitats, such as in microfluidic devices, microchambers and microreactors, the ecological and microbiological aspects must be considered. In such devices and experiments cells often live in structured environments that from an ecological viewpoint could be considered “patchy” (i.e. with strong spatial heterogeneities and variations in suitability for the cells).1 In such artificial habitats, the formation of a metapopulation, a set of interacting subpopulations, is observed along with a complex population dynamics.2 The ecological aspects are also manifested in the fact that cells compete for resources,3 which sometimes results in unexpected spatial distribution and growth of cells.4 In such biological scenarios, cell-cell communication is important.5 The complexity of the evolved communication mechanisms among prokaryotes can be distinguished by the various chemical signals used by the different bacterial species. Beside the known quorum sensing signaling molecules (homoserine lactones and oligopeptides6,7), bacteria use toxins (antibiotics, bacteriocins8), antimicrobial peptides,9 amino acids,10 exopolysaccharides,11 or metabolic waste products (indole11) as signaling molecules. These chemical signals have distinguishable targets and functions (intra-, or interspecies communication, inter-kingdom signaling), and they have a key role in the communication of bacterial populations in natural habitats. Motile bacteria have the great advantage of being able to explore the heterogeneous environment. By a mechanism called chemotaxis bacteria are able to sense concentration changes of certain chemicals, and swim towards increasing or decreasing concentrations of chemoattractants or chemorepellent molecules, respectively.13,14 It has been shown that signaling and chemotaxis may be coupled, and signaling molecules may act as chemoeffectors.5 Although traditional microbiology techniques enable us to study the interactions of bacterial communities on a large scale (such as co-culturing bacteria on agar plates or in shaken flasks), these traditional tools do not allow us to follow the dynamics and the fundamental mechanisms on single cell level. In the last few decades, the development of microengineering and nanotechnology has revealed new directions in traditional microbiology. Microfluidics has provided excellent tools for studying bacteria in controlled environments.15–18 Here we present experiments performed with microfluidic devices to study the interaction of physically separated but chemically coupled bacterial populations. These populations, growing in microchambers and channels separated by porous membranes, exhibit dynamic spatial rearrangements as a result of secreInteraction of Bacterial Populations in Coupled Microchambers

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