Biology subjects

Datta, S. S.

Publications and source records attributed to Datta, S. S..

14 recordsLinked to original sources

bioRxiv2026

Death & Chemotaxis: Bacterial chemotaxis enables collective escape from phage predation

Bacteriophages ("phage") are viruses that prey on bacteria in diverse environments, from biological tissues to soils. In many of these environments, bacterial hosts are constantly migrating, yet how bacterial migration is influenced by phage predation remains poorly understood. Using transparent granular hydrogels that mimic natural habitats, we directly visualize populations of motile Escherichia coli encountering lytic T4 phage. Unexpectedly, we find that even in phage-rich environments, bacteria successfully form chemotactic fronts that enable them to migrate over large distances without needing to develop phage resistance. Higher phage concentrations delay front formation but not steady-state front speed or shape. By combining our experiments with biophysical modeling, we demonstrate that this phenomenon arises from the ability of cells to collectively outrun trailing phage bursts--as quantified by a dimensionless "escape parameter" comparing chemotactic and predation rates. This work thus reveals and provides mechanistic insight into the role of cell motility in shaping phage-bacteria interactions in spatially-extended environments.

microbiology↗

bioRxiv2025

Naegleria amoebae seek confinement and crawl persistently through narrow spaces

The "brain-eating amoeba" Naegleria fowleri dwells in ponds where it normally feeds on bacteria, but if it enters the brain it can cause a deadly infection. To establish infection, N. fowleri must migrate through different environments--along olfactory axons, through openings in the cribriform plate, and within brain tissue--yet how it does so remains unknown. As a model for N. fowleri migration within these environments, we examine how its non-pathogenic relative, Naegleria gruberi, navigates environments of distinct geometries. We show that Naegleria uses both actin-rich protrusions and membrane blebs to crawl across or between flat surfaces. We also explore how Naegleria interact with narrow channels and find that, unlike Dictyostelium amoebae that we show frequently disengage from channel interfaces, Naegleria amoebae probe channels until they enter. Once inside, Naegleria crawls quickly (>50 m/min) and unidirectionally over long distances (>1 mm) using only bleb-based motility. We also introduced Naegleria to granular hydrogel matrices that mimic pond sediments and found that cells readily enter and migrate through these three-dimensional matrices using both blebs and lamellar protrusions. Although cells in matrices showed lower persistence at short timescales, longer time scales correlate with increased persistence, suggesting Naegleria cells may retain memory of past orientation. We propose that pond life may select for three behaviors that prime Naegleria for pathogenesis: memory-guided motility that would facilitate exploration of sinus cavities, confinement-seeking ("claustrophilia") that would promote entry into narrow passages along olfactory axons, and persistent bleb-based migration that would allow rapid transit along axons to the brain.

cell biology↗

bioRxiv2025

Soil texture regulates bacterial motility and chemotactic recruitment to plant roots

Soil microbial communities regulate critical ecological processes, including nutrient cycling, carbon sequestration, and plant growth. However, due to the opacity and structural complexity of soil, how physical constraints imposed by pore geometry in-fluence bacterial motility and chemotactic recruitment to plant roots remains poorly understood. We use a transparent soil mimic composed of cryolite grains that replicate the structural characteristics of natural soils while enabling direct visualization of bacterial dynamics. Using Escherichia coli as a model bacterium, we combine macroscopic spreading assays with microscopic tracking of cellular trajectories to characterize how soil texture affects motility across pore scales. We find that bacterial motility shifts from run-and-tumble behavior in large, open pores to frequent trapping in smaller, more confined spaces. This transition is governed by the pore size distribution and leads to reduced effective diffusivity and slower population-scale spreading. Moreover, pore-scale confinement hinders the chemotactic recruitment of bacteria to Arabidopsis thaliana roots: recruitment is robust in sandy and loamy soils but negligible in highly confining textures. Our results establish soil texture as a critical factor regulating microbial dynamics and ecological interactions in the rhizosphere. This mechanistic understanding complements genomic surveys by identifying physical confinement as an ecological filter that shapes root-associated microbiomes. These findings highlight the essential and previously underappreciated role of soil texture, suggesting new strategies for managing microbial communities to promote plant health and sustainable agriculture.

biophysics↗

bioRxiv2025

A nutrient bottleneck limits antibiotic efficacy in structured bacterial populations

Antibiotic resistance is a growing global health threat. Therefore, it is critically important to optimize how existing antibiotics act against bacterial infections. Although antibiotic activity is well studied at the single cell level, many infections are caused by spatially structured multicellular populations. In such populations, cellular consumption of scarce nutrients establishes strong spatial variations in their abundance. These nutrient variations have long been hypothesized to help bacterial populations tolerate antibiotics, since single-cell studies show that antibiotic tolerance depends on metabolic activity, and thus, local nutrient availability. Here, we directly test this hypothesis by visualizing cell death in Escherichia coli populations with defined structures upon exposure to nutrient (glucose) and antibiotic (fosfomycin). We find that nutrient availability acts as a bottleneck to antibiotic killing, causing death to propagate through the population as a traveling front--a phenomenon predicted over 20 years ago, but never verified until now. By integrating our measurements with biophysical theory and simulations, we establish quantitative principles that explain how collective nutrient consumption can limit the progression of this "death front," protecting a population from a nominally deadly antibiotic dose. While increasing nutrient supply can overcome this bottleneck, our work reveals that in some cases, excess nutrient can unexpectedly promote the regrowth of resistant cells. Altogether, this work provides a key step toward predicting and controlling antibiotic treatment of spatially structured bacterial populations, yielding fundamental biophysical insights into collective behavior and helping to guide strategies for more effective antibiotic stewardship.

biophysics↗

bioRxiv2025

Spatial self-organization of confined bacterial suspensions

Lab studies of bacteria usually focus on cells in spatially-extended, nutrient-replete settings, such as in liquid cultures and on agar surfaces. By contrast, many biological and environmental settings--ranging from mucus in the body to ocean sediments and the soil beneath our feet--feature multicellular bacterial populations that are confined to tight spots where essential metabolic substrates (e.g., oxygen) are scarce. What influence does such confinement have on a bacterial population? Here, we address this question by studying suspensions of motile Escherichia coli confined to quasi two-dimensional (2D) droplets. We find that when the droplet size and cell concentration are both large enough, the initially-uniform suspension spatially self-organizes into a concentrated, immotile inner "core" that coexists with a more dilute, highly-motile surrounding "shell". By simultaneously measuring cell concentration, oxygen concentration, and motility-generated fluid flow, we show that this behavior arises from the interplay between oxygen transport through the droplet from its boundary, uptake by the cells, and corresponding changes in their motility in response to oxygen variations. Furthermore, we use theory and simulations to develop quantitative principles describing this interplay--establishing a bio-physical framework that unifies all our experimental observations. Our work thereby sheds new light on the rich collective behaviors that emerge for bacterial populations, and other forms of chemically-reactive living and active matter, in confined environments, and provides a way to predict and control these behaviors more broadly.

biophysics↗

bioRxiv2024

Morphogenesis of bacterial colonies in polymeric environments

Many bacteria live in polymeric fluids, such as mucus, environmental polysaccharides, and extracellular polymers in biofilms. However, lab studies typically focus on cells in polymer-free fluids. Here, we show that interactions with polymers shape a fundamental feature of bacterial life--how they proliferate in space in multicellular colonies. Using experiments, we find that when polymer is sufficiently concentrated, cells generically and reversibly form large serpentine "cables" as they proliferate. By combining experiments with biophysical theory and simulations, we demonstrate that this distinctive form of colony morphogenesis arises from an interplay between polymer-induced entropic attraction between neighboring cells and their hindered ability to diffusely separate from each other in a viscous polymer solution. Our work thus reveals a pivotal role of polymers in sculpting proliferating bacterial colonies, with implications for how they interact with hosts and with the natural environment, and uncovers quantitative principles governing colony morphogenesis in such complex environments.

biophysics↗

bioRxiv2024

Influence of bacterial swimming and hydrodynamics on infection by phages

Bacteriophages ("phages") are viruses that infect bacteria. Since they do not actively self-propel, phages rely on thermal diffusion to find target cells--but can also be advected by fluid flows, such as those generated by motile bacteria themselves in bulk fluids. How does the flow field generated by a swimming bacterium influence how it encounters and is infected by phages? Here, we address this question using coupled molecular dynamics and lattice Boltzmann simulations of flagellated bacteria swimming through a bulk fluid containing uniformly-dispersed phages. We find that while swimming increases the rate at which both the cell body and flagellar propeller are infected by phages, hydrodynamic interactions strongly suppress this increase at the cell body, but conversely enhance this increase at the flagellar bundle. Our results highlight the pivotal influence of hydrodynamics on the interactions between bacteria and phages, as well as other diffusible species in microbial environments.

biophysics↗

bioRxiv2023

Interplay between environmental yielding and dynamic forcing regulates bacterial growth

Many bacterial habitats--ranging from gels and tissues in the body to cell-secreted exopolysaccharides in biofilms--are rheologically complex, undergo dynamic external forcing, and have unevenly-distributed nutrients. How do these features jointly influence how the resident cells grow and proliferate? Here, we address this question by studying the growth of Escherichia coli dispersed in granular hydrogel matrices with defined and highly-tunable structural and rheological properties, under different amounts of external forcing imposed by mechanical shaking, and in both aerobic and anaerobic conditions. Our experiments establish a general principle: that the balance between the yield stress of the environment that the cells inhabit{sigma} y and the external stress imposed on the environment{sigma} regulates bacterial growth by modulating transport of essential nutrients to the cells. In particular, when{sigma} y < {sigma}, the environment is easily fluidized and mixed over large scales, providing nutrients to the cells and sustaining complete cellular growth. By contrast, when{sigma} y > {sigma}, the elasticity of the environment suppresses large-scale fluid mixing, limiting nutrient availability and arresting cellular growth. Our work thus reveals a new mechanism, beyond effects that change cellular behavior via local forcing, by which the rheology of the environment may regulate microbial physiology in diverse natural and industrial settings.

biophysics↗

bioRxiv2023

Interfacial morphodynamics of proliferating microbial communities

In microbial communities, various cell types often coexist by occupying distinct spatial domains. What determines the shape of the interface between such domains--which in turn influences the interactions between cells and overall community function? Here, we address this question by developing a continuum model of a 2D spatially-structured microbial community with two distinct cell types. We find that, depending on the balance of the different cell proliferation rates and substrate friction coefficients, the interface between domains is either stable and smooth, or unstable and develops finger-like protrusions. We establish quantitative principles describing when these different interfacial behaviors arise, and find good agreement both with the results of previous experimental reports as well as new experiments performed here. Our work thus helps to provide a biophysical basis for understanding the interfacial morphodynamics of proliferating microbial communities, as well as a broader range of proliferating active systems.

biophysics↗

bioRxiv2023

Pattern formation by bacteria-phage interactions

The interactions between bacteria and phages--viruses that infect bacteria--play critical roles in agriculture, ecology, and medicine; however, how these interactions influence the spatial organization of both bacteria and phages remain largely unexplored. Here, we address this gap in knowledge by developing a theoretical model of motile, proliferating bacteria that aggregate via motility-induced phase separation (MIPS) and encounter phage that infect and lyse the cells. We find that the non-reciprocal predator-prey interactions between phage and bacteria strongly alter spatial organization, in some cases giving rise to a rich array of finite-scale stationary and dynamic patterns in which bacteria and phage coexist. We establish principles describing the onset and characteristics of these diverse behaviors, thereby helping to provide a biophysical basis for understanding pattern formation in bacteria-phage systems, as well as in a broader range of active and living systems with similar predator-prey or other non-reciprocal interactions.

biophysics↗

bioRxiv2022

Roughening instability of growing 3D bacterial colonies

How do growing bacterial colonies get their shapes? While colony morphogenesis is well-studied in 2D, many bacteria grow as large colonies in 3D environments, such as gels and tissues in the body, or soils, sediments, and subsurface porous media. Here, we describe a morphological instability exhibited by large colonies of bacteria growing in 3D. Using experiments in transparent 3D granular hydrogel matrices, we show that dense colonies of four different species of bacteria--Escherichia coli, Vibrio cholerae, Pseudomonas aeruginosa, and Komagataeibacter sucrofermentans--generically roughen as they consume nutrients and grow beyond a critical size, eventually adopting a characteristic branched, broccoli-like, self-affine morphology independent of variations in the cell type and environmental conditions. This behavior reflects a key difference between 2D and 3D colonies: while a 2D colony may access the nutrients needed for growth from the third dimension, a 3D colony inevitably becomes nutrient-limited in its interior, driving a transition to rough growth at its surface. We elucidate the onset of roughening using linear stability analysis and numerical simulations of a continuum model that treats the colony as an active fluid whose dynamics are driven by nutrient-dependent cellular growth. We find that when all dimensions of the growing colony substantially exceed the nutrient penetration length, nutrient-limited growth drives a 3D morphological instability that recapitulates essential features of the experimental observations. Our work thus provides a framework to predict and control the organization of growing colonies--as well as other forms of growing active matter, such as tumors and engineered living materials--in 3D environments.

biophysics↗

bioRxiv2022

Microbial mutualism generates multistable and oscillatory growth dynamics

Microbial communities typically comprise multiple different species with an intricate network of interactions, ranging from competitive to cooperative, between them. How does the nature of these inter-species interactions impact overall community behavior? While the influence of purely competitive interactions is well-studied, the opposite case of mutualistic interactions--which are also prevalent in many naturally-occurring communities--is poorly understood. Here, we address this gap in knowledge by mathematically modeling a well-mixed two-species community of aerobes and anaerobes having mutualistic metabolic interactions between them. Despite the simplicity of the model, we find that it reproduces three characteristic experimental findings. In particular, in response to changes in the fluxes of exogenously-supplied carbon and oxygen, the community adopts two distinct stable states with differing fractions of aerobes and anaerobes. These states are bistable, capable of arising under identical environmental conditions; transitions between the two are therefore history-dependent and can give rise to oscillations in the bacterial and chemical concentrations. Moreover, using the model, we establish biophysical principles describing how oxygen depletion and nutrient sharing jointly dictate the characteristics of the different states as well as the transitions between them. Altogether, this work thus helps disentangle and highlight the pivotal role of mutualism in governing the overall stability and functioning of microbial communities. Moreover, our model provides a foundation for future studies of more complex communities that play important roles in agriculture, environment, industry, and medicine.

systems biology↗

bioRxiv2020

Chemotactic Migration of Bacteria in Porous Media

Chemotactic migration of bacteria--their ability to direct multicellular motion along chemical gradients--is central to processes in agriculture, the environment, and medicine. However, studies are typically performed in homogeneous media, despite the fact that many bacteria inhabit heterogeneous porous media such as soils, sediments, and biological gels. Here, we directly visualize the migration of Escherichia coli populations in 3D porous media. We find that pore-scale confinement is a strong regulator of chemotactic migration. Strikingly, cells use a different primary mechanism to direct their motion in confinement than in bulk liquid. Further, confinement markedly alters the dynamics and morphology of the migrating population--features that can be described by a continuum model, but only when standard motility parameters are substantially altered from their bulk liquid values. Our work thus provides a framework to predict and control the migration of bacteria, and active matter in general, in heterogeneous environments. Statement of SignificanceTypical studies of bacterial motility focus on cells in homogeneous media; however, many bacteria inhabit tight porous media such as soils, sediments, and biological gels. This paper demonstrates how confinement in a porous medium fundamentally alters the chemotactic migration of Escherichia coli. We find that cells use a different primary mechanism to direct their motion in confinement than in bulk liquid. Further, confinement markedly alters the overall dynamics and morphology of a migrating population--features that can be described by a continuum model, but only when standard motility parameters are substantially altered from their bulk liquid values. This work thus provides a framework to predict and control the migration of bacteria, and active matter in general, in heterogeneous porous environments.

biophysics↗

bioRxiv2018

High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine

The lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms; however, little is understood about how this suspension is re-structured as it transits the gut. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluid ex vivo. We find that mucins and immunoglobulins are not required for aggregation. Instead, aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions, which do not require specific chemical interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut.

biophysics↗