Chia, N; et al.
Understanding how microbes gather into biofilm communities and maintain diversity remains one of the central questions of microbiology, requiring an understanding of microbes as communal rather then individual organisms. Phase variation plays an integral role in the formation of diverse phenotypes within biofilms. We propose a collective mechanism for phase variation based on gene transfer agents, and apply the theory to predict the population structure and growth dynamics of a biofilm. Our results describe quantitatively recent experiments, with the only adjustable parameter being the rate of intercellular horizontal gene transfer. Our approach derives from a more general picture for the emergence of cooperation between microbes.
Weitz JS; et al.
Viral lysis of microbial hosts releases organic matter that can then be assimilated by nontargeted microorganisms. Quantitative estimates of virus-mediated recycling of carbon in marine waters, first established in the late 1990s, were originally extrapolated from marine host and virus densities, host carbon content and inferred viral lysis rates. Yet, these estimates did not explicitly incorporate the cascade of complex feedbacks associated with virus-mediated lysis. To evaluate the role of viruses in shaping community structure and ecosystem functioning, we extend dynamic multitrophic ecosystem models to include a virus component, specifically parameterized for processes taking place in the ocean euphotic zone. Crucially, we are able to solve this model analytically, facilitating evaluation of model behavior under many alternative parameterizations. Analyses reveal that the addition of a virus component promotes the emergence of complex communities. In addition, biomass partitioning of the emergent multitrophic community is consistent with well-established empirical norms in the surface oceans. At steady state, ecosystem fluxes can be probed to characterize the effects that viruses have when compared with putative marine surface ecosystems without viruses. The model suggests that ecosystems with viruses will have (1) increased organic matter recycling, (2) reduced transfer to higher trophic levels and (3) increased net primary productivity. These model findings support hypotheses that viruses can have significant stimulatory effects across whole-ecosystem scales. We suggest that existing efforts to predict carbon and nutrient cycling without considering virus effects are likely to miss essential features of marine food webs that regulate global biogeochemical cycles.
Levin, BJ; et al
The human microbiome encodes vast numbers of uncharacterized enzymes, limiting our functional understanding of this community and its effects on host health and disease. By incorporating information about enzymatic chemistry into quantitative metagenomics, we determined the abundance and distribution of individual members of the glycyl radicalenzyme superfamily among the microbiomes of healthy humans. We identified many uncharacterized family members, including a universally distributed enzyme that enables commensal gut microbes and humanpathogens to dehydrate trans-4-hydroxy-l-proline, the product of the most abundant human posttranslational modification. This "chemically guided functional profiling" workflow can therefore use ecological context to facilitate the discovery of enzymes in microbial communities.
Khandelwal, RA; et al.
A central focus in studies of microbial communities is the elucidation of the relationships between genotype, phenotype, and dynamic communitystructure. Here, we present a new computational method called communityflux balance analysis (cFBA) to study the metabolic behavior of microbialcommunities. cFBA integrates the comprehensive metabolic capacities of individual microorganisms in terms of (genome-scale) stoichiometric models of metabolism, and the metabolic interactions between species in the community and abiotic processes. In addition, cFBA considers constraints deriving from reaction stoichiometry, reaction thermodynamics, and the ecosystem. cFBA predicts for communities at balanced growth the maximal community growth rate, the required rates of metabolic reactions within and between microbes and the relative species abundances. In order to predict species abundances and metabolic activities at the optimal community growth rate, a nonlinear optimization problem needs to be solved. We outline the methodology of cFBA and illustrate the approach with two examples of microbial communities. These examples illustrate two useful applications of cFBA. Firstly, cFBA can be used to study how specific biochemical limitations in reaction capacities cause different types of metabolic limitations that microbial consortia can encounter. In silico variations of those maximal capacities allow for a global view of the consortium responses to various metabolic and environmental constraints. Secondly, cFBA is very useful for comparing the performance of different metabolic cross-feeding strategies to either find one that agrees with experimental data or one that is most efficient for the community of microorganisms.
Liu J; et al.
Bacteria within communities can interact to organize their behavior. It has been unclear whether such interactions can extend beyond a single community to coordinate the behavior of distant populations. We discovered that two Bacillus subtilis biofilm communities undergoing metabolic oscillations can become coupled through electrical signaling and synchronize their growth dynamics. Coupling increases competition by also synchronizing demand for limited nutrients. As predicted by mathematical modeling, we confirm that biofilms resolve this conflict by switching from in-phase to antiphase oscillations. This results in time-sharing behavior, where each community takes turns consuming nutrients. Time-sharing enables biofilms to counterintuitively increase growth under reduced nutrient supply. Distant biofilms can thus coordinate their behavior to resolve nutrient competition through time-sharing, a strategy used in engineered systems to allocate limited resources.
Van Boeckel, TP; et al.
Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg−1, 148 mg⋅kg−1, and 172 mg⋅kg−1 for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.
Bucci V, et al.
The intestinal microbiota is an ecosystem susceptible to external perturbations such as dietary changes and antibiotic therapies. Mathematical models of microbial communities could be of great value in the rational design of microbiota-tailoring diets and therapies. Here, we discuss how advances in another field, engineering of microbial communities for wastewater treatment bioreactors, could inspire development of mechanistic mathematical models of the gut microbiota. We review the state of the art in bioreactor modeling and current efforts in modeling the intestinal microbiota. Mathematical modeling could benefit greatly from the deluge of data emerging from metagenomic studies, but data-driven approaches such as network inference that aim to predict microbiome dynamics without explicit mechanistic knowledge seem better suited to model these data. Finally, we discuss how the integration of microbiome shotgun sequencing and metabolic modeling approaches such as flux balance analysis may fulfill the promise of a mechanistic model.
This meeting is hosted by the Integrated Training in Microbial Systems (ITiMS) program at the University of Michigan and is sponsored by the Burroughs Wellcome Fund.