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Ion channels enable electrical communication in bacterial communities


The study of bacterial ion channels has provided fundamental insights into the structural basis of neuronal signalling; however, the native role of ion channels in bacteria has remained elusive. Here we show that ion channels conduct long-range electrical signals within bacterial biofilm communities through spatially propagating waves of potassium. These waves result from a positive feedback loop, in which a metabolic trigger induces release of intracellular potassium, which in turn depolarizes neighbouring cells. Propagating through the biofilm, this wave of depolarization coordinates metabolic states among cells in the interior and periphery of the biofilm. Deletion of the potassium channel abolishes this response. As predicted by a mathematical model, we further show that spatial propagation can be hindered by specific genetic perturbations to potassium channel gating. Together, these results demonstrate a function for ion channels in bacterial biofilms, and provide a prokaryotic paradigm for active, long-range electrical signalling in cellular communities.

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Figure 1: Biofilms produce synchronized oscillations in membrane potential.
Figure 2: Potassium release is involved in active signal propagation within the biofilm.
Figure 3: The molecular mechanism of signal propagation involves potassium channel gating.

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We would like to thank S. Lockless, K. Süel, R. Wollman, T. Çağatay and M. Elowitz for comments during the writing of the manuscript, and C. Piggott for cloning help. A.P. is a Simons Foundation Fellow of the Helen Hay Whitney Foundation. J.G.-O. is supported by the Ministerio de Economia y Competitividad (Spain) and FEDER, under project FIS2012-37655-C02-01, and by the ICREA Academia Programme. This research was funded by the National Institutes of Health, National Institute of General Medical Sciences Grant R01 GM088428 and the National Science Foundation Grant MCB-1450867 50867 (both to G.M.S.). This work was also supported by the San Diego Center for Systems Biology (NIH Grant P50 GM085764).

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Authors and Affiliations



G.M.S., A.P., J.L., M.A. and J.G.-O. designed the research, A.P. and J.L. performed the experiments, J.L. and A.P. performed the data analysis, J.G.O. performed the mathematical modelling, S.L. made the bacteria strains, and G.M.S., A.P., J.L. and J.G.-O. wrote the manuscript. All authors discussed the manuscript.

Corresponding author

Correspondence to Gürol M. Süel.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Thioflavin T (ThT) is a fluorescent reporter that is inversely related to the membrane potential.

a, ThT and DiSC3(5), an established reporter of membrane potential in bacteria23, both oscillate within biofilms. ThT has an approximately three fold higher sensitivity to changes in membrane potential compared to DiSC3(5). Sensitivity is defined as the ratio between peak height and error in peak height. Error bars indicate mean ± s.d. (n = 8 biofilm regions, averaged over the 4 pulses shown). b, The cellular ThT fluorescence depends on the external pH, where higher pH results in greater membrane potential, as expected24. ThT itself is insensitive to these pH changes and the traces are background subtracted to eliminate possible artefacts. Representative trace is selected from three independent biofilms. c, Oscillations in ThT and growth rate are inversely correlated, linking membrane potential oscillations to the metabolic cycle which produces periodic growth pauses18. Growth rate is calculated by taking the derivative of biofilm radius over time (Supplementary Information). Representative trace is selected from over 75 independent biofilms. d, Replacing glutamate with 0.2% glutamine, which eliminates the need to take up glutamate or retain ammonium, quenches ThT oscillations. This further suggests that ThT oscillations are specific to the metabolic cycle involving glutamate and ammonium. A representative trace was selected from three independent experiments.

Extended Data Figure 2 A fluorescent reporter of extracellular potassium (APG-4) indicates that potassium has a role in membrane potential oscillations.

a, High-resolution images showing the intracellular localization of ThT and primarily extracellular localization of APG-4 (top). Quantification of ThT and APG-4 along the 2 μm profile indicated in the phase image indicates that APG-4 does not significantly diffuse into the cell (bottom). Representative images are selected from six independent experiments. b, Induction curve for APG-4 generated using externally supplemented KCl. The experiment was repeated twice. c, Oscillations in extracellular potassium in the surrounding cell-free region during biofilm oscillations. These oscillations occurred during the experiment shown in Fig. 2b, c and the pulses are synchronized between the biofilm and the surrounding cell-free region. Representative trace is selected from six independent experiments. d, Induction curve for ANG-2 generated using externally supplemented NaCl. The experiment was repeated twice. e, Simultaneous measurement of ThT and ANG-2 indicates a lack of oscillations in extracellular sodium. Representative trace selected from three independent biofilms. f, Furthermore, perturbing extracellular sodium concentrations in the media had no detectable effect on membrane potential oscillations. A representative trace was selected from four independent experiments.

Extended Data Figure 3 Active propagation of potassium signal within the biofilm.

a, A chemical potassium clamp (300 mM KCl, matching the intracellular concentration29, and 30 μM valinomycin) prevents the formation of potassium electrochemical gradients across the cellular membrane. Valinomycin is an antibiotic that creates potassium-specific carriers in the cellular membrane32. b, Clamping net potassium flux quenches oscillations in membrane potential. A representative trace was selected from two independent biofilms. c, Propagation of extracellular potassium is estimated by tracking the half-maximal position of the pulse over time. Representative traces are shown for a single pulse selected from one of six independent experiments. d, Propagation of extracellular potassium is relatively constant over time in contrast to diffusion that is expected to decay. The diffusion line is calculated using the mean squared displacement (MSD) and the diffusion coefficient for potassium in biofilms (Supplementary Information). Slopes are calculated from the same representative data shown in c.

Extended Data Figure 4 External potassium affects the metabolic state of the cell.

a, A potassium shock (300 mM KCl) produces an initial ThT decrease (depolarization) followed by a period of sustained ThT increase (hyperpolarization). ThT is inversely related to the membrane potential. A corresponding pulse in APG-4 during this ThT increase suggests that hyperpolarization is due to release of potassium. APG-4 signal due to the external potassium shock itself was subtracted using the cell-free background near the biofilm. A representative trace was selected from three independent experiments. b, ThT spikes in response to external potassium shock (300 mM KCl) but not an equivalent shock of 300 mM sorbitol, an uncharged solute. A representative trace was selected from three independent experiments. c, The hyperpolarization response occurs when cells are grown in glutamate but not when glutamate is replaced by 0.2% glutamine, which bypasses the need to take up glutamate or retain ammonium. A representative trace was selected from four independent biofilms.

Extended Data Table 1 List of strains used in this study
Extended Data Table 2 Parameter values used in the model

Supplementary information

Supplementary Information

This file contains Supplementary Text and Data and Supplementary References. (PDF 682 kb)

Video 1: Global oscillations in membrane potential (ThT) in a growing biofilm.

Global oscillations in membrane potential (ThT) in a growing biofilm. (MP4 1478 kb)

Video 2: Waves of extracellular potassium (APG-4) in a growing biofilm.

Waves of extracellular potassium (APG-4) in a growing biofilm. (MP4 637 kb)

Video 3: Oscillations in membrane potential (ThT) in a wild type and yugOΔtrkA mutant biofilm

The yugOΔtrkA mutant strain lacks the gating domain for the YugO potassium channel and is unable to signal the edge of the biofilm. (MP4 348 kb)

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Prindle, A., Liu, J., Asally, M. et al. Ion channels enable electrical communication in bacterial communities. Nature 527, 59–63 (2015).

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