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Borse, F.

Publications and source records attributed to Borse, F..

3 recordsLinked to original sources

How far can microbial monocultures predict growth in multi-strain communities?

Previous research in microbes successfully predicted biculture growth based on monoculture growth curves. Still, the usual model-based approach does not seem to extend to communities involving more than two bacterial strains. Here, we use a model-blind machine-learning approach to predict community-wide yield, area under the growth curve, maximum relative growth rate and its timing in communities involving up to five strains of Escherichia coli. First, we identify the highest per-capita growth rate and its timing in monocultures as major predictors of multi-strain community growth. Next, we show that a random forest trained on communities involving a low number of strains is able to predict the outcomes of communities involving a higher number of strains. Finally, we reveal diminishing returns in using more and more complex communities in order to predict the behaviour of a higher-level community, because monoculture- and biculture-based growth predictions are often already accurate. This finding relativises the need for experiments involving high numbers of strains when studying the growth dynamics of multi-strain communities.

ecology↗

Quantifying massively parallel microbial growth with spatially mediated interactions

Quantitative understanding of microbial growth is an essential prerequisite for successful control of pathogens as well as various biotechnology applications. Even though the growth of cell populations has been extensively studied, microbial growth remains poorly characterized at the spatial level. Indeed, even isogenic populations growing at different locations on solid growth medium typically show significant location-dependent variability in growth. Here we show that this variability can be attributed to an interplay between populations interacting with their local environment and the diffusion of nutrients and energy sources coupling the environments, i.e. interpopulation interactions are mediated via the shared environment. We use a dual approach, first applying machine learning regression models to discover that location dominates growth variability at specific times, and, in parallel, developing explicit population growth models to describe this spatial effect. In particular, treating nutrient and energy source concentration as a latent variable allows us to develop a mechanistic resource consumer model that captures growth variability across the shared environment. As a consequence, we are able to determine intrinsic growth parameters for each local population, removing confounders common to location-dependent variability in growth. Importantly, our explicit low parametric model for the environment paves the way for massively parallel experimentation with configurable spatial niches for testing specific eco-evolutionary hypotheses. Author summaryImage-based platforms allow obtaining population size estimates for massively parallel growth experiments on substrate plates at relatively low cost. However, such population size data has been shown to display a high degree of spatial variability, which occurs even with isogenic populations. Here we first quantified the importance of spatial location on growth variation using a machine learning approach, and then developed spatially aware population growth models to explain the spatial structure of the growth data. Ultimately, we showed that a spatial consumer-resource model with local microhabitats connected via diffusion can fully explain the observed spatial variation in growth while allowing the inference of intrinsic growth parameters of specific populations. This result provides a method for systematic extraction of spatial growth models and paves the way for massively parallel eco-evolutionary experimentation.

ecology↗

Strong Selective Agents Determine Resistance Evolution in a Multidrug Therapeutic Regime

The impact of fitness landscape features on evolutionary outcomes has attracted considerable interest in recent decades. However, evolution often occurs under time-dependent selection in so-called fitness seascapes where the landscape is under flux. Fitness seascapes are an inherent feature of natural environments, where the landscape changes owing both to the intrinsic fitness consequences of previous adaptations and extrinsic changes in selected traits caused by new environments. The complexity of such seascapes may curb the predictability of evolution. However, empirical efforts to test this question utilising a comprehensive set of regimes are lacking. Here we employed an in vitro microbial model system to investigate differences in evolutionary outcomes between time-invariant and -dependent environments, including all possible temporal permutations, with three subinhibitory antimicrobials and a viral parasite (phage) as selective agents. Expectedly, time-invariant environments caused stronger directional selection for resistances compared to time-dependent environments. Intriguingly, however, multidrug resistance outcomes in both cases were largely driven by two strong selective agents (rifampicin and phage) out of four agents in total. These agents either caused cross-resistance or obscured the phenotypic effect of other resistance mutations, modulating the evolutionary outcome overall in time-invariant environments and as a function of exposure epoch in time-dependent environments. This suggests that identifying strong selective agents and their pleiotropic effects is critical for predicting evolution in fitness seascapes, with ramifications for evolutionarily informed strategies to mitigate drug resistance evolution.

evolutionary biology↗