Minimizing co-growth as a broad predictor of community robustness

bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-17

Microbial communities rarely remain in a fixed physiological state. Instead, they progress through internal life cycles in which changing metabolites, spatial organization, and physiological states reshape ecological interactions over time. Despite extensive theory on coexistence with fixed interactions, we lack simple quantitative predictors of robustness for communities undergoing repeated growth and dispersal cycles. Here we show that a single quantity, the temporal co-growth of community members, predicts robustness across several models of community maturation, including chemotactic spatial patterning, cross-feeding with toxicity, and a phenomenological many-species model with prescribed growth trajectories. Communities in which different species grow at distinct times persist far longer under stochastic reseeding than communities with overlapping growth, with average community lifetime increasing approximately exponentially as co-growth decreases. Across the systems studied here, diverse mechanisms such as spatial organization, metabolic cascades, and physiological programs promote robustness insofar as they reduce the temporal overlap of rapid growth across species. These results identify co-growth as a common quantitative feature of robust dynamically maturing communities and suggest that minimizing co-growth may provide a broader organizing principle for ecological robustness.

Hypersensitivity of chitin degradation to initial species densities due to monomer diffusion

Proceedings of the National Academy of Sciences · 2026-01-05

Resource competition strongly shapes microbial community dynamics and functionality. In polysaccharide-degrading communities, primary degraders release hydrolytic enzymes, whereas exploiters consume released products without producing enzyme themselves. We investigate the competitive strategies employed by marine chitin degraders and N-acetylglucosamine (GlcNAc) exploiters, revealing various mechanisms that impact community viability and growth dynamics. In addition to direct competition strategies such as antibiotic secretion or cell aggregation on chitin particles (which helps monopolize enzyme access), exploiters also inhibit degraders by diverting limiting GlcNAc flux during the early stages of particle degradation. This critical phase requires degraders to overcome the diffusive loss of GlcNAc to sustain their chitinase production. Through quantitative measurements and modeling, we demonstrate that nutrient competition among species and nutrient loss through diffusion during the initial stages of community dynamics strongly influence the long-term success of the community. The initial community composition dictates the former mechanisms, while the latter is closely related to particle size, both of which have profound implications for environmental carbon cycling. The resulting hypersensitivity of the community is analogous to the Allee effect observed in population biology, where the outcomes-in our case polymer degradation-are heavily dependent on starting conditions. This study sheds light on how metabolic competition in the early phases of particle degradation governs species interactions, resource partitioning, and overall community viability, even under identical environmental and genetic conditions.

Extrusion-modulated DnaA activity oscillations coordinate DNA replication with biomass growth

eLife · 2025-08-06

Robust control of DNA replication is fundamental to bacterial proliferation. In Escherichia coli , replication initiation is thought to be regulated by oscillations in DnaA activity, driven by DnaA-chromosome interactions that differ among leading models. However, direct evidence linking these oscillations to replication initiation has been lacking, and existing models fail to explain the observed decoupling of replication initiation from dnaA expression. Here, we establish a direct link between DnaA activity and replication initiation by demonstrating robust oscillations in DnaA activity, which peak precisely at replication initiation across diverse growth conditions and genetic perturbations. Notably, these oscillations persist even when dnaA transcription remains constant, suggesting a regulatory mechanism that modulates DnaA activity independently of its expression. Additionally, we propose an extrusion model in which DNA-binding proteins sense biomass-DNA imbalance and extrude DnaA from the chromosome to trigger replication, overcoming limitations of existing models. Consistent with this model, perturbation of the nucleoid-associated protein H-NS modulates DnaA activity and replication timing, supporting its mechanistic validity.

Distantly related bacteria share a rigid proteome allocation strategy with flexible enzyme kinetics

Proceedings of the National Academy of Sciences · 2025-04-29 · 13 citations

Bacteria are known to allocate their proteomes according to how fast they grow, and the allocation strategies employed strongly affect bacterial adaptation to different environments. Much of what is currently known about proteome allocation is based on extensive studies of the model organism Escherichia coli . It is not clear how much of E. coli ’s proteome allocation strategy is applicable to other species, particularly since different species can grow at vastly different rates even in the same growth condition. In this study, we investigate differences in nutrient-dependent proteome allocation programs adopted by several distantly related bacterial species, including Vibrio natriegens , one of the fastest-growing bacteria known. Extensive quantitative proteome characterization across conditions reveals an invariant allocation program in response to changing nutrients despite systemic, species-specific differences in enzyme kinetics. This invariant program is not organized according to the growth rate but is based on a common internal metric of nutrient quality after scaling away species-specific differences in enzyme kinetics, with the faster species behaving as if it is growing under a higher temperature. The flexibility of enzyme kinetics and the rigidity of proteome allocation programs across species defy common notions of evolvability and resource optimization. Our results suggest the existence of a blueprint of proteome allocation shared by diverse bacterial species, with implications on common underlying regulatory strategies. Further knowledge on the existence and organization of such phylogeny-transcending relations also promises to simplify the bottom–up description and understanding of bacterial behaviors in ecological communities.

Extrusion-modulated DnaA activity oscillations coordinate DNA replication with biomass growth

bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-13

Abstract Robust control of DNA replication is fundamental to bacterial proliferation. In Escherichia coli , replication initiation is thought to be regulated by oscillations in DnaA activity, driven by DnaA-chromosome interactions that differ among leading models. However, direct evidence linking these oscillations to replication initiation has been lacking, and existing models fail to explain the observed decoupling of replication initiation from dnaA expression. Here, we establish a direct link between DnaA activity and replication initiation by demonstrating robust oscillations in DnaA activity, which peak precisely at replication initiation across diverse growth conditions and genetic perturbations. Notably, these oscillations persist even when dnaA transcription remains constant, suggesting a regulatory mechanism that modulates DnaA activity independently of its expression. Additionally, we propose an extrusion model in which DNA-binding proteins sense biomass-DNA imbalance and extrude DnaA from the chromosome to trigger replication, overcoming limitations of existing models. Consistent with this model, perturbation of the nucleoid-associated protein H-NS modulates DnaA activity and replication timing, supporting its mechanistic validity.

Extrusion-modulated DnaA activity oscillations coordinate DNA replication with biomass growth

eLife · 2025-10-17

Abstract Robust control of DNA replication is fundamental to bacterial proliferation. In Escherichia coli, replication initiation is thought to be regulated by oscillations in DnaA activity, driven by DnaA-chromosome interactions that differ among leading models. However, direct evidence linking these oscillations to replication initiation has been lacking, and existing models fail to explain the observed decoupling of replication initiation from dnaA expression. Here, we establish a direct link between DnaA activity and replication initiation by demonstrating robust oscillations in DnaA activity, which peak precisely at replication initiation across diverse growth conditions and genetic perturbations. Notably, these oscillations persist even when dnaA transcription remains constant, suggesting a regulatory mechanism that modulates DnaA activity independently of its expression. Additionally, we propose an extrusion model in which DNA-binding proteins sense biomass-DNA imbalance and extrude DnaA from the chromosome to trigger replication, overcoming limitations of existing models. Consistent with this model, perturbation of the nucleoid-associated protein H-NS modulates DnaA activity and replication timing, supporting its mechanistic validity.

Dynamic coexistence driven by physiological transitions in microbial communities

Proceedings of the National Academy of Sciences · 2025-04-17 · 10 citations

Microbial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes in exponential growth often modify their environments so strongly that they are forced out of the growth state into stressed, nongrowing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory. Here, we introduce a phenomenological model, the Community State Model, to gain insight into the dynamic coexistence of microbes due to changes in their physiological states during cyclic succession. Our model specifies the growth preference of each species along a global ecological coordinate, taken to be the biomass density of the community, but is otherwise agnostic to specific interactions (e.g., nutrient starvation, stress, aggregation), in order to focus on self-consistency conditions on combinations of physiological states, "community states," in a stable ecosystem. We identify three key features of such dynamical communities that contrast starkly with steady-state communities: enhanced community stability through staggered dominance of different species in different community states, increased tolerance of community diversity to fast growing species dominating distinct community states, and increased requirement of growth dominance by late-growing species. These features, derived explicitly for simplified models, are proposed here as principles aiding the understanding of complex dynamical communities. Our model shifts the focus of ecosystem dynamics from bottom-up studies based on fixed, idealized interspecies interaction to top-down studies based on accessible macroscopic observables such as growth rates and total biomass density, enabling quantitative examination of community-wide characteristics.

Author response: Extrusion-modulated DnaA activity oscillations coordinate DNA replication with biomass growth

2025-11-18

Extrusion-modulated DnaA activity oscillations coordinate DNA replication with biomass growth

eLife · 2025-08-06

Abstract Robust control of DNA replication is fundamental to bacterial proliferation. In Escherichia coli, replication initiation is thought to be regulated by oscillations in DnaA activity, driven by DnaA-chromosome interactions that differ among leading models. However, direct evidence linking these oscillations to replication initiation has been lacking, and existing models fail to explain the observed decoupling of replication initiation from dnaA expression. Here, we establish a direct link between DnaA activity and replication initiation by demonstrating robust oscillations in DnaA activity, which peak precisely at replication initiation across diverse growth conditions and genetic perturbations. Notably, these oscillations persist even when dnaA transcription remains constant, suggesting a regulatory mechanism that modulates DnaA activity independently of its expression. Additionally, we propose an extrusion model in which DNA-binding proteins sense biomass-DNA imbalance and extrude DnaA from the chromosome to trigger replication, overcoming limitations of existing models. Consistent with this model, perturbation of the nucleoid-associated protein H-NS modulates DnaA activity and replication timing, supporting its mechanistic validity.

Growth in Low Carbon Conditions Reveals Amino-Acid-Coupled Iron Uptake

bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-16

Abstract Bacteria in nature encounter substrates at widely varying concentrations, yet studies of bacterial physiology have focused more on nutrient type than concentration, partly due to challenges in maintaining low concentrations. We developed a Millifluidic Continuous Culture Device (MCCD) to culture bacteria under precisely controlled nutrient conditions, including very low concentrations, in a manner suitable for proteomic analysis. Using the MCCD, we cultured Escherichia coli with a mixture of amino acids as the sole carbon source at three concentrations supporting growth rates spanning a fivefold range. Surprisingly, at the lowest concentration, cells exhibited proteomic signatures of iron shortage despite equal iron levels across conditions. We observed the uptake of labeled iron-histidine and iron-cysteine complexes, indicating that amino acids facilitated iron acquisition and that amino-acid-bound iron is bioavailable to E. coli . These findings reveal a previously unknown mechanism of bacterial iron acquisition that emerged under the flow imposed by the MCCD, which likely diluted the siderophore pool and reduced their efficacy. This work highlights the importance of studying bacterial physiology under low nutrient concentrations and demonstrates how physical conditions, such as flow, shape microbial nutrient acquisition strategies.