Biology subjects

Mitarai, N.

Publications and source records attributed to Mitarai, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Interplay of mechanics, growth and viral infection dynamics in a spatially expanding bacterial colony

We investigate the dynamics of the spread of the infection due to a phage- during the range expansion of an E coli colony. We find a rich panoply of spatio-temporal dynamics at large colony-level length scales, arising due to the interplay of mechanical forces, growth and viral infection dynamics at smaller cellular length scales. Strikingly, the phages "surf" the front of the growing bacterial colony by hitchhiking on E coli that are advected due to the growth of bacteria in the colony, resulting in an anisotropic spread of the phages. We identify microscopic processes - of the phage release during lysis (occurring on short millisecond timescales at length scales close to that of a single bacterium) and local nematic alignment of the rod-like E coli bacteria (occurring on timescales comparable to the bacterial growth rate and the length scales of a few bacterial cells) - that enhance the advective effects driving the hitchhiking behavior. Combining our experiments with a mathematical model, we explain the multiple spatio-temporal dynamical regimes - from the coexistence of uninfected bacteria, resistant (lysogenic) cells and phages, to fixed points where the entire population turns resistant or remains uninfected. Our work broaches a new frontier in the investigation of eco-evolutionary processes arising from the mechanical and ecological forces due to the interactions between viruses and their hosts.

biophysics↗

bioRxiv2026

Multivalent Surface Search Dynamics Shape Bacteriophage Adsorption Efficiency: A Stochastic Model of Tail Fiber Optimization

Phages must locate and bind to bacterial surface receptors to initiate infection. Their tail fiber configuration critically influences this process. We develop a stochastic model describing surface search as a renewal process, incorporating attachment, detachment, and target-finding steps. Using both numerical simulations and analytical calculations, we quantify how tail fiber number, attachment-detachment rates, and geometric constraints impact the mean and the distribution of time to successful adsorption. Notably, the search efficiency shows a nonmonotonic dependence on tail fibers number, governed by a trade-off between binding stability and diffusion-mediated mobility. This optimum shifts depending on the effective bacterial density, target radius, and fiber reach. Short fiber reach imposes severe geometric constraints, reducing mobility at high tail fiber counts and leading to performance degradation. Our findings suggest that phage adsorption strategies are shaped by a balance between anchoring and exploration, with evolutionary implications for tail fiber design and infection efficiency. SIGNIFICANCEBacteriophages typically use tail fibers to bind and explore bacterial surfaces. Using stochastic modeling and numerical simulations, we uncover how attachment-detachment kinetics and tail fiber geometry shape surface search efficiency. Our results reveal a trade-off: more tail fibers stabilize attachment but hinder exploration, especially with short reattachment ranges. These findings offer a mechanistic basis for understanding how phages optimize infection strategies and may explain the diversity of tail architectures observed in nature.

biophysics↗

bioRxiv2026

Pushing for survival: Spatial intermixing and indirect resistance enable collective growth

The survival of bacterial communities depends on complex dynamics at molecular, cellular, and ecosystem levels. Understanding antibiotic resistance requires a broader community context, as emergent dynamics can lead to unexpected outcomes, such as the persistence of susceptible populations or community collapse. We capture these behaviors by integration of microscopy and mathematical modeling to understand how bacterial interactions and spatial organization shape bacteriostatic antibiotic resistance in a two-strain community. We show that local chloramphenicol detoxification and mechanical pushing shape bacterial coexistence and spatial organization, promoting the survival and growth of otherwise susceptible bacteria. Additionally, the timing of antibiotic administration critically determines the growth dynamics, co-existence, local diversity of susceptible and resistant bacteria, and overall community resistance. Together, these insights highlight how community-level interactions fundamentally reshape antibiotic responses and open new avenues to understand and control bacterial resilience. SIGNIFICANCE STATEMENTAntibiotic resistance is usually treated as a property of individual bacterial strains, yet bacteria typically grow in dense, spatially structured communities where physical interactions matter. We find that under bacteriostatic (growth pausing) antibiotic stress, resistant bacteria can create highly localized protective environments that allow sensitive cells to survive and proliferate. This protection arises not only from antibiotic detoxification, but also from growth-driven mechanical pushing that maintains close cell-cell proximity. As a result, antibiotic tolerance emerges as a collective, spatially dependent property rather than an intrinsic trait of single cells. These findings show that spatial organization, physical forces, and treatment timing can strongly reshape therapy outcomes, with implications for how resistance is understood and managed in microbial communities.

biophysics↗

bioRxiv2025

Wrinkles emerge from matrix complementarity in heterogenous biofilms

Biofilms are dynamic communities of microorganisms encased in a self-produced extracellular matrix. These resilient structures pose challenges across nearly all human activities, from healthcare to industry. The mechanical behaviour of a biofilm is shaped by the heterogenous composition of its matrix, both spatially and chemically. In turn, these mechanics influence the biofilms architecture at micro- and macroscopic scales, driving its complexity and adaptability. Morphologically, this is reflected in mechanical deformations of the biofilm known as wrinkles. In nature, biofilms often host different species of bacteria, allowing for a great diversity of matrix components. Here, we use a combination of two Escherichia coli strains as a model for a multispecies biofilm in which each bacterial strain produces one of two complementary matrix fibres: an amyloid protein (curli) or a polysaccharide (phosphoethanolamine-cellulose). Using fluorescence microscopy, we confirm that the two bacterial strains rapidly segregate into isogenic sectors, decreasing local heterogeneity. Furthermore, we show how wrinkles form, both in the homogenous central region of the biofilm, as well as at the boundary between sectors (i.e. where the two matrix producers co-localize). Finally, we show that increasing strain intermixing via the addition of bacteriophages results in thicker, taller wrinkles, irrespective of whether the two fibres are produced by two different strains or co-produced by the same bacteria.

biophysics↗

bioRxiv2025

Host Physiology Dependent Lysis Timing Shapes Bacteriophage Competition Under Nutrient Fluctuations

When bacteriophages infect starved host bacteria, the restrictive host physiology may lead to prolonged latent periods and/or reduced burst sizes, compared to infection of a fast-growing bacterium. Using a mathematical model, we explore a system of two types of virulent phages that have distinct host physiology dependencies and are infecting a shared bacterial host population. We consider different environmental regimes to test whether they can compete and coexist under fluctuating conditions, putting emphasis on phases with limited resources for bacterial growth. We find that the fitness of a phage that can modulate lysis timing in response to changes in the host physiology is elevated in fluctuating feast-famine environments compared to more stable environments which favor rapid lysis with a reduced burst size. This effect is closely coupled to the increased mortality of free phages due to abortive adsorption to already infected host bacteria during starvation phases. We identify specific system dynamics that either support or suppress the propagation of the delayed lysis phage. This theoretical analysis highlights the competitive benefits and limitations of lysis delay as a phage propagation strategy. Our results underscore the importance of considering the bacterial physiology dependence of bacteriophage replication in order to correctly predict phage fitness and population dynamics in complex environments. IMPORTANCEBacteriophage replication depends strongly on the physiological state of the host, yet most ecological and theoretical studies treat phage life histories as fixed traits. This overlooks how nutrient limitation, starvation, and fluctuating growth conditions reshape infection outcomes. By examining competition between phages with different responses to host physiology, our work shows how environmentally driven changes in the latent period can alter which phages persist, spread, or are lost. These insights clarify when delayed lysis is a beneficial strategy and when it becomes a liability. More broadly, our results highlight the need to integrate host physiology into models of phage-host dynamics to better understand microbial ecosystems and to guide applications such as rational phage therapy design.

microbiology↗

bioRxiv2025

Stochastic Emergence of Irregular Infection Fronts in Motile Bacteria-Phage Populations

Interactions between bacteriophages and motile bacteria can produce irregular spatial patterns. Here we show that these irregularities arise from stochastic infection dynamics at the single-cell level. We develop a discrete, stochastic model of phage-bacteria co-propagation, which represents bacteria and phage numbers as non-negative integers on a two-dimensional lattice, while nutrients and attractants are treated as real-valued fields. Stochastic rules govern bacterial growth, chemotactic movement, infection, and lysis, allowing spatial heterogeneity to emerge in agreement with experimentally observed asymmetric patterns. Simulations reveal that rare events, in which an infected bacterium migrates ahead of the front before lysis, locally seed new infection centers. The resulting front roughness is controlled by the product of burst size and adsorption rate, and is suppressed when the effective population size per lattice site increases or the variability of latent period decreases. These results link microscopic stochasticity to emergent spatial structure in phage-bacteria populations.

ecology↗

bioRxiv2025

Superinfections Shape Collective Lysis Dynamics in T-Even Phage Infections: Insights from an Individual-Based Model

Bacteria infected by T-even bacteriophages exhibit a variety of multiplicity of infection (MOI) dependent behaviours, including lysis from without (LO), cell lysis induced by an exceptionally high number of secondary adsorptions, and lysis inhibition (LIN), a phenomenon in which host cell lysis is delayed as the same bacterium adsorbs multiple phages. We propose an individual-based model that captures these MOI-dependent dynamics phenomenologically. The model takes into account the development of LO resistance (LOR) after the primary infection, and LIN is modelled by a fixed average delay in latent period per secondary adsorption with stochastic variability. The model successfully reproduces the experimentally observed multiple peaks in phage production following controlled phage addition. We extend the model to simulate batch culture growth and demonstrate that synchronized collapse of LINed culture can emerge as a collective phenomenon when LOR cells have a high, but finite, LO threshold (LOR cell lysis from withOut, LORO). Finally, we apply the model to a spatially structured bacterial colony under phage attack. We find that, if the burst size is comparable to the LO thresholds, especially LORO may play a role in colony survival due to locally elevated MOI near lysing cells. These results highlight the importance of spatial dynamics and secondary adsorption thresholds in phage-host population outcomes.

systems biology↗

bioRxiv2025

Viral Infection Depends on Host's Metabolism

Viral infection begins with attachment to host surface structures such as receptors, pili, or porins. While prior research has focused on structural compatibility and recognition, the role of host physiology, particularly metabolic state, on viral commitment to infection remains underexplored. Here, we measured the adsorption rates () of five Escherichia coli phages representing various life cycles and entry pathways under controlled metabolic conditions. Four phages showed significantly reduced adsorption under energy-limited states, with weaker-binding phages being more sensitive. Using E. coli and its phages allowed us to institute a number of control infections that would be difficult with other organisms. Our findings support a two-step infection model where bound phages may disengage under unfavorable conditions, reducing commitment to non-productive infections. We observed a correlation between adsorption rates under energy-competent conditions and sensitivity to host metabolic state. Our results highlight host physiology as a key factor in virus-host interactions under energy-limited conditions.

microbiology↗

bioRxiv2025

Triggered and Spontaneous Dormancy in Bacteria During Feast-Famine Cycles with Stochastic Antibiotic Application

Bacteria can enter dormancy triggered by stress, such as starvation. When stress is removed, a large part of the population will exhibit some lag time before regrowth. It has been observed that even under stress-free conditions that allow for exponential growth, a small subpopulation can spontaneously enter dormancy temporarily. The dormant population often survives antibiotic application because many types of antibiotics target the cell growth and division process. If bacteria are in an environment where antibiotics are sometimes applied, the population can evolve to adjust their dormancy frequency to better survive antibiotics without losing too much of the population growth. Here, we consider the situation in which antibiotics are applied stochastically during repeated feast-famine cycles. We analyse the best strategy for long-term growth when the bacteria are allowed to tune both the lag time at the start of the feast period and the spontaneous dormancy in the feast period. We show that spontaneous dormancy can provide an advantage only when the antibiotic application and the start of the feast period are decoupled. When the triggered dormant and spontaneous dormant states are treated as different states and the antibiotic addition time is fixed, the optimal strategy is either triggered or spontaneous dormancy. Exhibiting both types of dormancy is optimal only when there is a certain level of stochastic fluctuation in the antibiotic application timing.

systems biology↗

bioRxiv2024

Self-organized coexistence of phage and a population of host colonies

Phages and bacteria coexist under widely different conditions, ranging from liquid cultures to oceans, soil, and the human gut. However, our models are typically limited to well-mixed liquid cultures governed by mass-action kinetics. Here, we suggest a modification to the Lotka-Volterra dynamics by including the formation of microcolonies. By analyzing the model in an open system with a steady influx of bacteria, we predict that the colony size distribution is power-low distributed with steeper exponents for the stronger external influx. In the realistic case where the phage attack rate to individual colonies is proportional to their radius, we obtain self-organization to a steady state where the maximal colony size is smaller for stronger external driving.

ecology↗

bioRxiv2024

Competitive advantages of secondary adsorption-triggered lysis inhibition for T-even phages

T-even bacteriophages are known to employ lysis inhibition (LIN), where the lysis of an infected host is delayed in response to secondary adsorptions. Upon the eventual burst of the host, significantly more phage progenies are released. Here, we analysed the competitive advantage of LIN using a mathematical model. In batch culture, LIN provides a bigger phage yield at the end of the growth where all the hosts are infected due to an exceeding number of phage particles and, in addition, gives a competitive advantage against LIN mutants with rapid lysis by letting them adsorb to already infected hosts in the LIN state. By simulating plaque formation in a spatially structured environment, we show that, while LIN phages will produce a smaller zone of clearance, the area over which the phages spread is actually comparable to those without LIN. The analysis suggests that LIN induced by secondary adsorption is favourable in terms of competition, both in spatially homogeneous and inhomogeneous environments. Author SummaryT-even bacteriophages can delay the lysis of their hosts when they detect more phages are adsorbing to the hosts, increasing the progeny production per host. Using a mathematical model, we provide a quantitative analysis of this strategys competitive advantages and disadvantages in different environments. The model predicts that phage adsorption to lysis-inhibited cells provides a significant competitive advantage to lysis-inhibiting phage against phages that quickly lyse the cells. We also find that secondary infection-triggered delay does not hinder the spreading of the phage in a lawn of uninfected cells, even though the apparent plaque size is small. The analysis suggests that lysis inhibition provides a robust competitive advantage for a virulent phage.

microbiology↗

bioRxiv2024

Cell aspect ratio is a mechanical winning strategy in microbial competition

Bacterial competition shapes community architecture, yet a universally conserved determinant remains elusive. We show that cell aspect ratio -a simple morphological feature- confers a competitive advantage. Using growth-based range expansion experiments, we show that longer bacteria conquer the expanding front, even when initially in minority. Using an agent-based model of dividing bacteria, to isolate the effect of aspect ratio, we reveal that the takeover mechanism is collective alignment: groups of locally aligned bacteria form "nematic arms" bridging the central region of the colony to the expanding front. Once at the front, bacteria align parallel to it and block shorter bacteria from access to nutrients and space. We confirm this observation with single-cell experiments and further generalise our findings by introducing a generic continuum model of alignment-dominated competition, explaining both experimental and cell-based model observations. Moreover, we extend our predictions to spherical range expansions and confirm the competitive advantage, even though the effect is less pronounced than in surface-attached colonies. Our results uncover a simple, yet hitherto overlooked, mechanical mechanism determining the outcome of bacterial competition, which is potentially ubiquitous among various bacteria. Current advances in genetic engineering enable aspect ratio tuning as a mechanism with broad implications for biofilm control.

biophysics↗

bioRxiv2023

Simple bacterial growth model for the formation of spontaneous and triggered dormant subpopulations

Bacterial persistence is a phenomenon where a subpopulation of cells can survive antibiotic treatment, and it is often linked to extremely slow growth or a dormant state. However, the mechanisms and factors that govern dormancy are not well understood. We propose a simplified growth model that treats the main cellular components as discrete variables and allocates resources among them according to different strategies. The model can reproduce some of the observed features of bacterial persistence, such as wide distribution in division times, long division times after a nutrient down-shift, and the existence of different dormant phenotypes. We also show how the growth structure, i.e., whether cells grow in a lineage or a branch, affects the dormant cells occurrence and distribution due to the growth states mother-daughter correlation. Our model provides a framework to explore the complex interactions between cellular processes and environmental conditions that lead to bacterial persistence.

systems biology↗

bioRxiv2023

Genetic mixing and demixing on expanding spherical frontiers

Genetic fluctuation during range expansion is a key process driving evolution. When a bacterial population is expanding on a 2D surface, random fluctuations in the growth of the pioneers at the front line cause a strong de-mixing of genotypes. Even when there is no selective advantage, sectors of low genetic diversity are formed. Experimental studies of range expansions in surface-attached colonies of fluorescently-labeled microorganisms have contributed significantly to our understanding of fundamental evolutionary dynamics. However, experimental studies on genetic fluctuations in 3D range expansions have been sparse, despite their importance for tumour or biofilm development. We encapsulated populations of two fluorescent Escherichia coli strains in inoculation droplets (volumes [~]0.1 nl). The confined ensemble of cells grew when embedded in a hydrogel - with nutrients - and developed 3D colonies with well-defined, sector-like regions. Using a confocal laser scanning microscope (CLSM), we imaged the development of 3D colonies and the emergence of sectors. We characterised how cell concentration in the inoculation droplet controls sectors, growth rate, and the transition from branched colonies to quasi-spherical colonies. We further analysed how sectors on the surface change over time. We complement these experimental results with a modified 3D Eden growth model. The model in 3D spherical growth predicts a phase, where sectors are merging, followed by a steady increase (constant rate), and the experimentally analysed sectors were consistent with this prediction. Ergo, our results demonstrate qualitative differences between radial (2D) and spherical (3D) range expansions and their importance in gene fixation processes.

biophysics↗

bioRxiv2023

A Systems Level Explanation for Gompertzian Mortality Patterns is provided by the "Multiple and Inter-dependent Component Cause Model"

Understanding and facilitating healthy aging has become a major goal in medical research and it is becoming increasingly acknowledged that there is a need for understanding the aging phenotype as a whole rather than focusing on individual factors. Here, we provide a universal explanation for the emergence of Gompertzian mortality patterns using a systems approach to describe aging in complex organisms that consist of many inter-dependent subsystems. Our model relates to the Sufficient-Component Cause Model, widely used within the field of epidemiology, and we show that including inter-dependencies between subsystems and modeling the temporal evolution of subsystem failure results in Gompertizan mortality on the population level. Our model also provides temporal trajectories of mortality-risk for the individual. These results may give insight into understanding how biological age evolves stochastically within the individual, and how this in turn leads to a natural heterogeneity of biological age in a population.

systems biology↗

bioRxiv2023

The dynamics of phage predation on a microcolony

Phage predation is an important factor for controlling the bacterial biomass. At face value, dense microbial habitats are expected to be vulnerable to phage epidemics due to the abundance of fresh hosts immediately next to any infected bacteria. Despite this, the bacterial microcolony is a common habitat for bacteria in nature. Here we experimentally quantify the fate of microcolonies of Escherichia coli exposed to virulent phage T4. It has been proposed that the outer bacterial layers of the colony will shield the inner layers from the phage invasion and thereby constrain the phage to the colonys surface. We develop a dynamical model that incorporates this shielding mechanism and fits the results with experimental measurements to extract important phage-bacteria interaction parameters. The analysis suggests that, while the shielding mechanism delays phage attack,T4 phage are able to diffuse so deep into the dense bacterial environment that colony level survival of the bacterial community is challenged. SignificanceThe shielding mechanism of bacterial microcolonies against phage invasion has been experimentally quantified, and the result was analyzed by using a mathematical model. The analysis suggests that while forming a dense colony delays phage attack by limiting the infection closer to the colony surface,T4 phage can diffuse so deep into the dense bacterial environment that colony-level survival of the bacterial community is challenged. This finding highlights the importance of the interplay between the phage infection dynamics and the physical structure of bacterial colonies in controlling the microbial population.

microbiology↗

bioRxiv2022

Motility mediates satellite formation in confined biofilms

Bacteria have spectacular survival capabilities and can spread in many, vastly different environments. For instance, when pathogenic bacteria infect a host, the cells expand through proliferation and squeezing through narrow pores and elastic matrices. However, the exact role of surface structures and matrix elasticity in colony expansion and morphogenesis is still largely unknown. Here we show how satellite colonies emerge around biofilms embedded in semi-soft agar in controlled in vitro assays. We tested how extra-cellular structures - important for biofilm formation and motility - control this morphology. Moreover, we identify the range of extra-cellular matrix elasticity, where this morphology is possible. When paralleled with mathematical modelling, our results demonstrate that satellite formation allows bacterial communities to spread faster. We anticipate that this strategy is important to speed up expansion in various environments while retaining the close interactions and protection provided by the community.

biophysics↗

bioRxiv2022

Structural determinants of relaxation dynamics in chemical reaction networks

Understanding the relationship between the structure of chemical reaction networks and their reaction dynamics is essential for unveiling the design principles of living organisms. However, while some network-structural features are known to relate to the steady-state characteristics of chemical reaction networks, mathematical frameworks describing the links between out-of-steady-state dynamics and network structure are still underdeveloped. Here, we characterize the out-of-steady-state behavior of a class of artificial chemical reaction networks consisting of the ligation and splitting reactions of polymers. Within this class, we examine minimal networks that can convert a given set of inputs (e.g., nutrients) to a specified set of targets (e.g., biomass precursors). We find three distinct types of relaxation dynamics after perturbation from a steady-state: exponential-, power-law-, and plateau-dominated. We computationally show that we can predict this out-of-steady-state dynamical behavior from just three features computed from the networks stoichiometric matrix, namely, (i) the rank gap, determining the existence of a steady-state; (ii) the left null-space, being related to conserved quantities in the dynamics; and (iii) the stoichiometric cone, dictating the range of achievable chemical concentrations. We further demonstrate that these three quantities also predict the type of relaxation dynamics of combinations of our minimal networks, larger networks with many redundant pathways, and a real example of a metabolic network. The unified method to predict the qualitative features of the relaxation dynamics presented here can provide a basis for understanding the design of metabolic reaction networks as well as industrially useful chemical production pathways. Author summaryThe relationship between network structure and chemical reaction dynamics is of central interest in chemical reaction network theory, as it underlies chemical manufacturing, cellular metabolism, and bioengineering. The links between structure and steady-state properties have been extensively investigated. However, how far the network structure determines the out-of-steady-state, transient dynamics of chemical reactions is unexplored. Here we construct a chemical reaction network model that is simple but generates a wide variety of network instances. By computationally exploring the networks structural- and dynamical features, we found that three network-structural features are sufficient to predict the qualitative characteristics of the relaxation dynamics after the chemical concentrations are perturbed from their steady-state. Depending on the values of those three features, the chemical reaction dynamics on the network exhibit exponential, plateau, and power-law relaxation. Also, we found that such features are determinants of the dynamics of biological metabolic reaction systems. Our findings provide a foundation for the structure-based prediction of chemical reaction dynamics.

systems biology↗