Biology subjects

Suel, G. M.

Publications and source records attributed to Suel, G. M..

3 recordsLinked to original sources

bioRxiv2026

Antibiotic condensates activate magnesium signaling to drive drug tolerance

The spatial distribution of small molecules within cells shapes their biological activity, yet these distributions are generally assumed to be governed passively by reaction-driven electrochemical gradients. Here we show that aminoglycoside antibiotics actively control their own subcellular organization by undergoing phase separation with RNAs. Combining in vitro reconstitution, bacterial assays, and molecular dynamics simulations, we discovered that aminoglycosides coacervate with RNA through multivalent electrostatic interactions, displacing and releasing RNA-bound Mg2+. This condensate-dependent Mg2+ release remodels the cytosolic labile Mg2+ pool and activates magnesium signaling. This effect dampens the magnesium-starvation regulation, sustains ribosome activity, and shifts the cellular electrochemical state, promoting bacterial fitness. Because condensation occurs only above a defined concentration threshold, it generates a non-monotonic dose-response in which higher antibiotic concentrations paradoxically enhance bacterial survival. This antibiotic condensate-dependent Mg2+ signaling confers tolerance to multiple ribosome-targeting antibiotics simultaneously even in cells lacking resistance gene, while condensate dissolution restores antibiotic efficacy. Our findings establish antibiotic-driven phase separation as a previously unrecognized mechanism to encode cellular signaling and identify antibiotic condensates as a distinct functional unit underlying drug tolerance.

microbiology↗

bioRxiv2022

Computational model of fractal interface formation in bacterial biofilms

Bacteria benefit from cellular heterogeneity: cells differentiate into diverse gene expression states. As colonies grow, cellular phenotypes arrange into spatial patterns. To uncover the functional role of these emergent patterns, we must understand how they arise from cellular growth and mechanical interactions. Here we present a simple, agent-based model to predict patterns of motile and extracellular matrix-producing cells in biofilms of Bacillus subtilis. By incorporating phenotypic inheritance, mechanical interactions, and peripheral motile cell dispersal, our model predicts the emergence of a pattern: matrix cells surround a fractal-like interior motile population. We find that, while some properties of the motile-matrix interface depend on initial conditions, the motile distribution at large radii depends solely on the models growth mechanism. The phenotypic interface exhibits a fractal dimension that increases as biofilms grow but reaches a maximum as the peripheral layer of matrix cells exceeds the capacity of the inner cells to push it out of the way. By varying parameters, we find correlations between the interface fractal dimension and expansion of motile cells. We validate findings using experiments on B. subtilis biofilms in microfluidics. Our model demonstrates the emergence of colony-level phenotypes from single cell-level interactions and cells modifying their own environment.

biophysics↗

bioRxiv2019

Metabolic basis of brain-like electrical signalling in bacterial communities

Information processing in the mammalian brain relies on a careful regulation of the mem-brane potential dynamics of its constituent neurons, which propagates across the neuronal tissue via electrical signalling. We recently reported the existence of electrical signalling in a much simpler organism, the bacterium Bacillus subtilis. In dense bacterial communi-ties known as biofilms, nutrient-deprived B. subtilis cells in the interior of the colony use electrical communication to transmit stress signals to the periphery, which interfere with the growth of peripheral cells and reduce nutrient consumption, thereby relieving stress from the interior. Here we explicitly address the interplay between metabolism and elec-trophysiology in bacterial biofilms, by introducing a spatially-extended mathematical model that combines the metabolic and electrical components of the phenomenon in a discretised reaction-diffusion scheme. The model is experimentally validated by environmental and ge-netic perturbations, and confirms that metabolic stress is transmitted through the bacterial population via a potassium wave. Interestingly, this behaviour is reminiscent of cortical spreading depression in the brain, characterised by a wave of electrical activity mediated by potassium diffusion that has been linked to various neurological disorders, calling for future studies on the evolutionary link between the two phenomena.

systems biology↗