Biology subjects

Obeng, N.

Publications and source records attributed to Obeng, N..

5 recordsLinked to original sources

bioRxiv2023

Environmental selection overrides host selection in a horizontally acquired microbiota

Horizontally acquired symbionts need to succeed both within hosts and the free-living environment. Microbes might invest differentially in these habitats, thus shaping fitness within host-associated microbiota communities. In this study, we investigated how host and environmental selection affect microbiota composition in a two-member model community of Pseudomonas lurida MYb11 and Ochrobactrum vermis MYb71 from the natural microbiota of Caenorhabditis elegans. Fitness characterizations in the host and non-host environment revealed distinct ecological strategies: while MYb11 dominated free-living by rapidly growing, it was quickly outcompeted within worms by MYb71. Using mathematical modeling and experimental evolution, we assessed how these distinct strategies affect microbiota composition over time. We found that MYb11 enriches in the host via its advantage in the environment and additionally adapts to the host. This community shift was mirrored in host fitness. Overall, this highlights the importance of the symbiont pool and shows that environmental selection can overwhelm host adaptation.

evolutionary biology↗

bioRxiv2023

Bacterial c-di-GMP plays a key role in the evolution of host-association

Most microbes evolve faster than their hosts and should therefore drive evolution of host-microbe interactions1-3. However, relatively little is known about the characteristics that define the adaptive path of microbes to host-association. In this study we have identified microbial traits that mediate adaptation to hosts by experimentally evolving the bacterium Pseudomonas lurida with the nematode Caenorhabditis elegans. We repeatedly observed the evolution of beneficial host-specialist bacteria with improved persistence in the nematode, achieved by mutations that uniformly upregulate the universal second messenger c-di-GMP. We subsequently upregulated c-di-GMP in different Pseudomonas species, consistently causing increased host-association. Comparison of Pseudomonad genomes from various environments revealed that c-di-GMP underlies adaptation to a variety of hosts, from plants to humans, suggesting that it is fundamental for establishing host-association.

evolutionary biology↗

bioRxiv2023

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

1.The microbiome is increasingly receiving attention as an important modulator of host health and disease. However, while numerous mechanisms through which the microbiome influences its host have been identified, there is still a lack of approaches that allow to specifically modulate the abundance of individual microbes or microbial functions of interest. Moreover, current approaches for microbiome manipulation such as fecal transfers often entail a non-specific transfer of entire microbial communities with potentially unwanted side effects. To overcome this limitation, we here propose the concept of precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In a first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we present a metabolic modeling network framework that allows us to define precision prebiotics for a two-member C. elegans microbiome model community comprising the immune-protective Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. Thus, we predicted compounds that specifically boost the abundance of the host-beneficial MYb11, four of which were experimentally validated in vitro (L-serine, L-threonine, D-mannitol, and {gamma}-aminobutyric acid). L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that constraint-based metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.

systems biology↗

bioRxiv2021

Modeling host-associating microbes under selection

The concept of fitness is often reduced to a single component, such as the replication rate in a given habitat. For species with complex life cycles, this can be an unjustified oversimplification, as every step of the life cycle can contribute to reproductive success in a specific way. In particular, this applies to microbes that spend part of their life cycles associated to a host, i.e. in a microbiota. In this case, there is a selection pressure not only on the replication rates, but also on the phenotypic traits associated to migrating from the external environment to the host and vice-versa. Here, we investigate a simple model of a microbial population living, replicating, migrating and competing in and between two compartments: a host and its environment. We perform a sensitivity analysis on the global growth rate to determine the selection gradient experienced by the microbial population. We focus on the direction of selection at each point of the phenotypic space, defining an optimal way for the microbial population to increase its fitness. We show that microbes can adapt to the two-compartment life cycle through either changes in replication or migration rates, depending on the initial values of the traits, the initial distribution of the population across the compartments, the intensity of competition, and the time scales involved in the life cycle versus the time scale of adaptation (which determines the adequate probing time to measure fitness). Overall, our model provides a conceptual framework to study the selection on microbes experiencing a host-associated life cycle.

evolutionary biology↗

bioRxiv2019

The functional repertoire encoded within the native microbiome of the model nematode Caenorhabditis elegans

The microbiome is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of the bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiome of the model nematode Caenorhabditis elegans. We integrated whole genome sequences of 77 bacterial microbiome members with metabolic modelling and experimental characterization of bacterial physiology. We found that, as a community, the microbiome can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses further revealed that nutrient context can influence how bacteria interact within the microbiome. We identified key bacterial traits that are likely to influence the microbes ability to colonize C. elegans (e.g., pyruvate fermentation to acetoin) and the resulting effects on nematode fitness (e.g., hydroxyproline degradation). Considering that the microbiome is usually neglected in the comprehensive research on this nematode, the resource presented here will help our understanding of C. elegans biology in a more natural context. Our integrative approach moreover provides a novel, general framework to dissect microbiome-mediated functions.

microbiology↗