Overcoming toxicity: why boom-and-bust cycles are good for non-antagonistic microbes.

Antagonistic interactions are critical determinants of microbial community stability and composition, offering host benefits such as pathogen protection and providing avenues for antimicrobial control. While the ability to eliminate competitors confers an advantage to antagonistic microbes, it often incurs a fitness cost. Consequently, many microbes only produce toxins or engage in antagonistic behavior in response to specific cues like population density or environmental stress. In laboratory settings, antagonistic microbes typically dominate over sensitive ones, raising the question of why both antagonistic and non-antagonistic microbes are found in natural environments and host microbiomes. Here, using both theoretical models and experiments with killer strains of Saccharomyces cerevisiae , we show that boom-and-bust dynamics caused by temporal environmental fluctuations can favor non-antagonistic microbes that do not incur the growth rate cost of toxin production. Additionally, using control theory, we derive bounds on the competitive performance and identify optimal regulatory toxin-production strategies in various boom-and-bust environments where population dilutions occur either deterministically or stochastically over time. Our findings offer a new perspective on how both antagonistic and non-antagonistic microbes can thrive under varying environmental conditions.

Segatella copri strains adopt distinct roles within a single individual's gut.

Segatella copri is a dominant member of individuals' gut microbiomes worldwide, especially in non-Western populations. Although metagenomic assembly and genome isolation have shed light on the genetic diversity of S. copri, the lack of available isolates from this clade has resulted in a limited understanding of how members' genetic diversity translates into phenotypic diversity. Within the confines of a single gut microbiome, we have isolated 63 strains from diverse lineages of S. copri. We performed comparative analyses that exposed differences in cellular morphologies, preferences in polysaccharide utilization, yield of short-chain fatty acids, and antibiotic resistance across isolates. We further show that exposure to S. copri lineages either evokes strong or muted transcriptional responses in human intestinal epithelial cells. Our study exposes large phenotypic differences within related S. copri isolates, extending this to host-microbe interactions.

A high throughput array microhabitat platform reveals how light and nitrogen colimit the growth of algal cells.

A mechanistic understanding of algal growth is essential for maintaining a sustainable environment in an era of climate change and population expansion. It is known that algal growth is tightly controlled by complex interactive physical and chemical conditions. Many mathematical models have been proposed to describe the relation of algal growth and environmental parameters, but experimental verification has been difficult due to the lack of tools to measure cell growth under precise physical and chemical conditions. As such, current models depend on the specific testing systems, and the fitted growth kinetic constants vary widely for the same organisms in the existing literature. Here, we present a microfluidic platform where both light intensity and nutrient gradients can be well controlled for algal cell growth studies. In particular, light shading is avoided, a common problem in macroscale assays. Our results revealed that light and nitrogen colimit the growth of algal cells, with each contributing a Monod growth kinetic term in a multiplicative model. We argue that the microfluidic platform can lead towards a general culture system independent algal growth model with systematic screening of many environmental parameters. Our work advances technology for algal cell growth studies and provides essential information for future bioreactor designs and ecological predictions.

Optimal Adaptive Testing for Epidemic Control: Combining Molecular and Serology Tests.

Epidemic interventions based on surveillance testing programs are a fundamental tool to control the first stages of new epidemics, yet they are costly, invasive and rely on scarce resources, limiting their applicability. To overcome these challenges, we investigate two optimal control problems: (i) how testing needs can be minimized while maintaining the number of infected individuals below a desired threshold, and (ii) how peak infections can be minimized given a typically scarce testing budget. We find that in both cases the optimal testing policy for the well-known Susceptible-Infected-Recovered (SIR) model is adaptive, with testing rates that depend on the epidemic state, and leads to significant cost savings compared to non-adaptive policies. By using the concept of observability, we then show that a central planner can estimate the required unknown epidemic state by complementing molecular tests, which are highly sensitive but have a short detectability window, with serology tests, which are less sensitive but can detect past infections.

Colimitation of light and nitrogen on algal growth revealed by an array microhabitat platform.

Microalgae are key players in the global carbon cycle and emerging producers of biofuels. Algal growth is critically regulated by its complex microenvironment, including nitrogen and phosphorous levels, light intensity, and temperature. Mechanistic understanding of algal growth is important for maintaining a balanced ecosystem at a time of climate change and population expansion, as well as providing essential formulations for optimizing biofuel production. Current mathematical models for algal growth in complex environmental conditions are still in their infancy, due in part to the lack of experimental tools necessary to generate data amenable to theoretical modeling. Here, we present a high throughput microfluidic platform that allows for algal growth with precise control over light intensity and nutrient gradients, while also performing real-time microscopic imaging. We propose a general mathematical model that describes algal growth under multiple physical and chemical environments, which we have validated experimentally. We showed that light and nitrogen colimited the growth of the model alga Chlamydomonas reinhardtii following a multiplicative Monod kinetic model. The microfluidic platform presented here can be easily adapted to studies of other photosynthetic micro-organisms, and the algal growth model will be essential for future bioreactor designs and ecological predictions.

Experimental evolution of dispersal: Unifying theory, experiments and natural systems.

Dispersal is a central life history trait that affects the ecological and evolutionary dynamics of populations and communities. The recent use of experimental evolution for the study of dispersal is a promising avenue for demonstrating valuable proofs of concept, bringing insight into alternative dispersal strategies and trade-offs, and testing the repeatability of evolutionary outcomes. Practical constraints restrict experimental evolution studies of dispersal to a set of typically small, short-lived organisms reared in artificial laboratory conditions. Here, we argue that despite these restrictions, inferences from these studies can reinforce links between theoretical predictions and empirical observations and advance our understanding of the eco-evolutionary consequences of dispersal. We illustrate how applying an integrative framework of theory, experimental evolution and natural systems can improve our understanding of dispersal evolution under more complex and realistic biological scenarios, such as the role of biotic interactions and complex dispersal syndromes.

Time-Dependent Biosensor Fluorescence as a Measure of Bacterial Arsenic Uptake Kinetics and Its Inhibition by Dissolved Organic Matter.

Microbe-mediated transformations of arsenic (As) often require As to be taken up into cells prior to enzymatic reaction. Despite the importance of these microbial reactions for As speciation and toxicity, understanding of how As bioavailability and uptake are regulated by aspects of extracellular water chemistry, notably dissolved organic matter (DOM), remains limited. Whole-cell biosensors utilizing fluorescent proteins are increasingly used for high-throughput quantification of the bioavailable fraction of As in water. Here, we present a mathematical framework for interpreting the time series of biosensor fluorescence as a measure of As uptake kinetics, which we used to evaluate the effects of different forms of DOM on uptake of trivalent arsenite. We found that thiol-containing organic compounds significantly inhibited uptake of arsenite into cells, possibly through the formation of aqueous complexes between arsenite and thiol ligands. While there was no evidence for competitive interactions between arsenite and low-molecular-weight neutral molecules (urea, glycine, and glyceraldehyde) for uptake through the aquaglyceroporin channel GlpF, which mediates transport of arsenite across cell membranes, there was evidence that labile DOM fractions may inhibit arsenite uptake through a catabolite repression-like mechanism. The observation of significant inhibition of arsenite uptake at DOM/As ratios commonly encountered in wetland pore waters suggests that DOM may be an important control on the microbial uptake of arsenite in the environment, with aspects of DOM quality playing an important role in the extent of inhibition. IMPORTANCE The speciation and toxicity of arsenic in environments like rice paddy soils and groundwater aquifers are controlled by microbe-mediated reactions. These reactions often require As to be taken up into cells prior to enzymatic reaction, but there is limited understanding of how microbial arsenic uptake is affected by variations in water chemistry. In this study, we explored the effect of dissolved organic matter (DOM) quantity and quality on microbial As uptake, with a focus on the role of thiol functional groups that are well known to form aqueous complexes with arsenic. We developed a quantitative framework for interpreting fluorescence time series from whole-cell biosensors and used this technique to evaluate effects of DOM on the rates of microbial arsenic uptake. We show that thiol-containing compounds significantly decrease rates of As uptake into microbial cells at environmentally relevant DOM/As ratios, revealing the importance of DOM quality in regulating arsenic uptake, and subsequent biotransformation, in the environment.

Antagonism between killer yeast strains as an experimental model for biological nucleation dynamics.

Antagonistic interactions are widespread in the microbial world and affect microbial evolutionary dynamics. Natural microbial communities often display spatial structure, which affects biological interactions, but much of what we know about microbial antagonism comes from laboratory studies of well-mixed communities. To overcome this limitation, we manipulated two killer strains of the budding yeast Saccharomyces cerevisiae, expressing different toxins, to independently control the rate at which they released their toxins. We developed mathematical models that predict the experimental dynamics of competition between toxin-producing strains in both well-mixed and spatially structured populations. In both situations, we experimentally verified theory's prediction that a stronger antagonist can invade a weaker one only if the initial invading population exceeds a critical frequency or size. Finally, we found that toxin-resistant cells and weaker killers arose in spatially structured competitions between toxin-producing strains, suggesting that adaptive evolution can affect the outcome of microbial antagonism in spatial settings.

Constrained proteome allocation affects coexistence in models of competitive microbial communities.

Microbial communities are ubiquitous and play crucial roles in many natural processes. Despite their importance for the environment, industry and human health, there are still many aspects of microbial community dynamics that we do not understand quantitatively. Recent experiments have shown that the structure and composition of microbial communities are intertwined with the metabolism of the species that inhabit them, suggesting that properties at the intracellular level such as the allocation of cellular proteomic resources must be taken into account when describing microbial communities with a population dynamics approach. In this work, we reconsider one of the theoretical frameworks most commonly used to model population dynamics in competitive ecosystems, MacArthur's consumer-resource model, in light of experimental evidence showing how proteome allocation affects microbial growth. This new framework allows us to describe community dynamics at an intermediate level of complexity between classical consumer-resource models and biochemical models of microbial metabolism, accounting for temporally-varying proteome allocation subject to constraints on growth and protein synthesis in the presence of multiple resources, while preserving analytical insight into the dynamics of the system. We first show with a simple experiment that proteome allocation needs to be accounted for to properly understand the dynamics of even the simplest microbial community, i.e. two bacterial strains competing for one common resource. Then, we study our consumer-proteome-resource model analytically and numerically to determine the conditions that allow multiple species to coexist in systems with arbitrary numbers of species and resources.

Microfluidic and mathematical modeling of aquatic microbial communities.

Aquatic microbial communities contribute fundamentally to biogeochemical transformations in natural ecosystems, and disruption of these communities can lead to ecological disasters such as harmful algal blooms. Microbial communities are highly dynamic, and their composition and function are tightly controlled by the biophysical (e.g., light, fluid flow, and temperature) and biochemical (e.g., chemical gradients and cell concentration) parameters of the surrounding environment. Due to the large number of environmental factors involved, a systematic understanding of the microbial community-environment interactions is lacking. In this article, we show that microfluidic platforms present a unique opportunity to recreate well-defined environmental factors in a laboratory setting in a high throughput way, enabling quantitative studies of microbial communities that are amenable to theoretical modeling. The focus of this article is on aquatic microbial communities, but the microfluidic and mathematical models discussed here can be readily applied to investigate other microbiomes.

Dynamic metabolic adaptation can promote species coexistence in competitive microbial communities.

Microbes are capable of physiologically adapting to diverse environmental conditions by differentially varying the rates at which they uptake different nutrients. In particular, microbes can switch hierarchically between different energy sources, consuming first those that ensure the highest growth rate. Experimentally, this can result in biphasic growth curves called "diauxic shifts" that typically arise when microbes are grown in media containing several nutrients. Despite these observations are well known in microbiology and molecular biology, the mathematical models generally used to describe the population dynamics of microbial communities do not account for dynamic metabolic adaptation, thus implicitly assuming that microbes cannot switch dynamically from one resource to another. Here, we introduce dynamic metabolic adaptation in the framework of consumer-resource models, which are commonly used to describe competitive microbial communities, allowing each species to temporally change its preferred energy source to maximize its own relative fitness. We show that dynamic metabolic adaptation enables the community to self-organize, allowing several species to coexist even in the presence of few resources, and to respond optimally to a time-dependent environment, thus showing that dynamic metabolic adaptation could be an important mechanism for maintaining high levels of diversity even in environments with few energy sources. We show that introducing dynamic metabolic strategies in consumer-resource models is necessary for reproducing experimental growth curves of the baker's yeast Saccharomyces cerevisiae growing in the presence of two carbon sources. Even though diauxic shifts emerge naturally from the model when two resources are qualitatively very different, the model predicts that the existence of such shifts is not a prerequisite for species coexistence in competitive communities.

Generalized size scaling of metabolic rates based on single-cell measurements with freshwater phytoplankton.

Kleiber's law describes the scaling of metabolic rate with body size across several orders of magnitude in size and across taxa and is widely regarded as a fundamental law in biology. The physiological origins of Kleiber's law are still debated and generalizations of the law accounting for deviations from the scaling behavior have been proposed. Most theoretical and experimental studies of Kleiber's law, however, have focused on the relationship between the average body size of a species and its mean metabolic rate, neglecting intraspecific variation of these 2 traits. Here, we propose a theoretical characterization of such variation and report on proof-of-concept experiments with freshwater phytoplankton supporting such framework. We performed joint measurements at the single-cell level of cell volume and nitrogen/carbon uptake rates, as proxies of metabolic rates, of 3 phytoplankton species using nanoscale secondary ion mass spectrometry (NanoSIMS) and stable isotope labeling. Common scaling features of the distribution of nutrient uptake rates and cell volume are found to hold across 3 orders of magnitude in cell size. Once individual measurements of cell volume and nutrient uptake rate within a species are appropriately rescaled by a function of the average cell volume within each species, we find that intraspecific distributions of cell volume and metabolic rates collapse onto a universal curve. Based on the experimental results, this work provides the building blocks for a generalized form of Kleiber's law incorporating intraspecific, correlated variations of nutrient-uptake rates and body sizes.

On the probabilistic nature of the species-area relation.

The Species-Area Relation (SAR), which describes the increase in the number of species S with increasing area A, is under intense scrutiny in contemporary ecology, in particular to probe its reliability in predicting the number of species going extinct as a direct result of habitat loss. Here, we focus on the island SAR, which is measured across a set of disjoint habitat patches, and we argue that the SAR portrays an average trend around which fluctuations are to be expected due to the stochasticity of community dynamics within the patches, external perturbations, and habitat heterogeneity across different patches. This probabilistic interpretation of the SAR, though already implicit in the theory of island biogeography and manifest in the scatter of data points in plots of empirical SAR curves, has not been investigated systematically from the theoretical point of view. Here, we show that the two main contributions to SAR fluctuations, which are due to community dynamics within the patches and to habitat heterogeneity between different patches, can be decoupled and analyzed independently. To investigate the community dynamics contribution to SAR fluctuations, we explore a suite of theoretical models of community dynamics where the number of species S inhabiting a patch emerges from diverse ecological and evolutionary processes, and we compare stationary predictions for the coefficient of variation of S, i.e. the fluctuations of S with respect to the mean. We find that different community dynamics models diverge radically in their predictions. In island biogeography and in neutral frameworks, where fluctuations are only driven by the stochasticity of diversification and extinction events, relative fluctuations decay when the mean increases. Computational evidence suggests that this result is robust in the presence of competition for space or resources. When species compete for finite resources, and mass is introduced as a trait determining species' birth, death and resource consumption rates based on empirical allometric scalings, relative fluctuations do not decay with increasing mean S due to the occasional introduction of new species with large resource demands causing mass extinctions in the community. Given this observation, we also investigate the contribution of external disturbance events to fluctuations of S in neutral community dynamics models and compare this scenario with the community dynamics in undisturbed non-neutral models. Habitat heterogeneity within a single patch, in the context of metapopulation models, causes variability in the number of coexisting species which proves negligible with respect to that caused by the stochasticity of the community dynamics. The second contribution to SAR fluctuations, which is due to habitat heterogeneity among different patches, introduces corrections to the coefficient of variation of S. Most importantly, inter-patches heterogeneity introduces a constant, lower bound on the relative fluctuations of S equal to the coefficient of variation of a habitat variable describing the heterogeneity among patches. Because heterogeneity across patches is inevitably present in natural ecosystems, we expect that the relative fluctuations of S always tend to a constant in the limit of large mean S or large patch area A, with contributions from community dynamics, inter-patches heterogeneity or both. We provide a theoretical framework for modelling these two contributions and we show that both can affect significantly the fluctuations of the SAR.

Physical interactions reduce the power of natural selection in growing yeast colonies.

Microbial populations often assemble in dense populations in which proliferating individuals exert mechanical forces on the nearby cells. Here, we use yeast strains whose doubling times depend differently on temperature to show that physical interactions among cells affect the competition between different genotypes in growing yeast colonies. Our experiments demonstrate that these physical interactions have two related effects: they cause the prolonged survival of slower-growing strains at the actively-growing frontier of the colony and cause faster-growing strains to increase their frequency more slowly than expected in the absence of physical interactions. These effects also promote the survival of slower-growing strains and the maintenance of genetic diversity in colonies grown in time-varying environments. A continuum model inspired by overdamped hydrodynamics reproduces the experiments and predicts that the strength of natural selection depends on the width of the actively growing layer at the colony frontier. We verify these predictions experimentally. The reduced power of natural selection observed here may favor the maintenance of drug-resistant cells in microbial populations and could explain the apparent neutrality of interclone competition within tumors.

The scaling structure of the global road network.

Because of increasing global urbanization and its immediate consequences, including changes in patterns of food demand, circulation and land use, the next century will witness a major increase in the extent of paved roads built worldwide. To model the effects of this increase, it is crucial to understand whether possible self-organized patterns are inherent in the global road network structure. Here, we use the largest updated database comprising all major roads on the Earth, together with global urban and cropland inventories, to suggest that road length distributions within croplands are indistinguishable from urban ones, once rescaled to account for the difference in mean road length. Such similarity extends to road length distributions within urban or agricultural domains of a given area. We find two distinct regimes for the scaling of the mean road length with the associated area, holding in general at small and at large values of the latter. In suitably large urban and cropland domains, we find that mean and total road lengths increase linearly with their domain area, differently from earlier suggestions. Scaling regimes suggest that simple and universal mechanisms regulate urban and cropland road expansion at the global scale. As such, our findings bear implications for global road infrastructure growth based on land-use change and for planning policies sustaining urban expansions.

Covariations in ecological scaling laws fostered by community dynamics.

Scaling laws in ecology, intended both as functional relationships among ecologically relevant quantities and the probability distributions that characterize their occurrence, have long attracted the interest of empiricists and theoreticians. Empirical evidence exists of power laws associated with the number of species inhabiting an ecosystem, their abundances, and traits. Although their functional form appears to be ubiquitous, empirical scaling exponents vary with ecosystem type and resource supply rate. The idea that ecological scaling laws are linked has been entertained before, but the full extent of macroecological pattern covariations, the role of the constraints imposed by finite resource supply, and a comprehensive empirical verification are still unexplored. Here, we propose a theoretical scaling framework that predicts the linkages of several macroecological patterns related to species' abundances and body sizes. We show that such a framework is consistent with the stationary-state statistics of a broad class of resource-limited community dynamics models, regardless of parameterization and model assumptions. We verify predicted theoretical covariations by contrasting empirical data and provide testable hypotheses for yet unexplored patterns. We thus place the observed variability of ecological scaling exponents into a coherent statistical framework where patterns in ecology embed constrained fluctuations.

Experimental evidence for strong stabilizing forces at high functional diversity of aquatic microbial communities.

Unveiling the mechanisms that promote coexistence in biological communities is a fundamental problem in ecology. Stable coexistence of many species is commonly observed in natural communities. Most of these natural communities, however, are composed of species from multiple trophic and functional groups, while theory and experiments on coexistence have been focusing on functionally similar species. Here, we investigated how functional diversity affects the stability of species coexistence and productivity in multispecies communities by characterizing experimentally all pairwise species interactions in a pool of 11 species of eukaryotes (10 protists and one rotifer) belonging to three different functional groups. Species within the same functional group showed stronger competitive interactions compared to among-functional group interactions. This often led to competitive exclusion between species that had higher functional relatedness, but only at low levels of species richness. Communities with higher functional diversity resulted in increased species coexistence and community biomass production. Our experimental findings and the results of a stochastic model tailored to the experimental interaction matrix suggest the emergence of strong stabilizing forces when species from different functional groups interact in a homogeneous environment. By combining theoretical analysis with experiments we could also disentangle the relationship between species richness and functional diversity, showing that functional diversity per se is a crucial driver of productivity and stability in multispecies community.

Sample and population exponents of generalized Taylor's law.

Taylor's law (TL) states that the variance V of a nonnegative random variable is a power function of its mean M; i.e., V = aM(b). TL has been verified extensively in ecology, where it applies to population abundance, physics, and other natural sciences. Its ubiquitous empirical verification suggests a context-independent mechanism. Sample exponents b measured empirically via the scaling of sample mean and variance typically cluster around the value b = 2. Some theoretical models of population growth, however, predict a broad range of values for the population exponent b pertaining to the mean and variance of population density, depending on details of the growth process. Is the widely reported sample exponent b ≃ 2 the result of ecological processes or could it be a statistical artifact? Here, we apply large deviations theory and finite-sample arguments to show exactly that in a broad class of growth models the sample exponent is b ≃ 2 regardless of the underlying population exponent. We derive a generalized TL in terms of sample and population exponents b(jk) for the scaling of the kth vs. the jth cumulants. The sample exponent b(jk) depends predictably on the number of samples and for finite samples we obtain b(jk) ≃ k = j asymptotically in time, a prediction that we verify in two empirical examples. Thus, the sample exponent b ≃ 2 may indeed be a statistical artifact and not dependent on population dynamics under conditions that we specify exactly. Given the broad class of models investigated, our results apply to many fields where TL is used although inadequately understood.

Generalized receptor law governs phototaxis in the phytoplankton Euglena gracilis.

Phototaxis, the process through which motile organisms direct their swimming toward or away from light, is implicated in key ecological phenomena (including algal blooms and diel vertical migration) that shape the distribution, diversity, and productivity of phytoplankton and thus energy transfer to higher trophic levels in aquatic ecosystems. Phototaxis also finds important applications in biofuel reactors and microbiopropellers and is argued to serve as a benchmark for the study of biological invasions in heterogeneous environments owing to the ease of generating stochastic light fields. Despite its ecological and technological relevance, an experimentally tested, general theoretical model of phototaxis seems unavailable to date. Here, we present accurate measurements of the behavior of the alga Euglena gracilis when exposed to controlled light fields. Analysis of E. gracilis' phototactic accumulation dynamics over a broad range of light intensities proves that the classic Keller-Segel mathematical framework for taxis provides an accurate description of both positive and negative phototaxis only when phototactic sensitivity is modeled by a generalized "receptor law," a specific nonlinear response function to light intensity that drives algae toward beneficial light conditions and away from harmful ones. The proposed phototactic model captures the temporal dynamics of both cells' accumulation toward light sources and their dispersion upon light cessation. The model could thus be of use in integrating models of vertical phytoplankton migrations in marine and freshwater ecosystems, and in the design of bioreactors.

Complex interaction of dendritic connectivity and hierarchical patch size on biodiversity in river-like landscapes.

Habitat fragmentation and land use changes are causing major biodiversity losses. Connectivity of the landscape or environmental conditions alone can shape biodiversity patterns. In nature, however, local habitat characteristics are often intrinsically linked to a specific connectivity. Such a link is evident in riverine ecosystems, where hierarchical dendritic structures command related scaling on habitat capacity. We experimentally disentangled the effect of local habitat capacity (i.e., the patch size) and dendritic connectivity on biodiversity in aquatic microcosm metacommunities by suitably arranging patch sizes within river-like networks. Overall, more connected communities that occupy a central position in the network exhibited higher species richness, irrespective of patch size arrangement. High regional evenness in community composition was found only in landscapes preserving geomorphological scaling properties of patch sizes. In these landscapes, some of the rarer species sustained regionally more abundant populations better tracking their own niche requirements compared to landscapes with homogeneous patch size or landscapes with spatially uncorrelated patch size. Our analysis suggests that altering the natural link between dendritic connectivity and patch size strongly affects community composition and population persistence at multiple scales. The experimental results are demonstrating a principle that can be tested in theoretical metacommunity models and eventually be projected to real riverine ecosystems.