Caenorhabditis elegans foraging patterns follow a simple rule of thumb.

Rules of thumb are behavioral algorithms that approximate optimal behavior while lowering cognitive and sensory costs. One way to reduce these costs is by simplifying the representation of the environment: While the theoretically optimal behavior may depend on many environmental variables, a rule of thumb may use a smaller set of variables that performs reasonably well. Experimental proof of this simplification requires an exhaustive mapping of all relevant combinations of several environmental parameters, which we performed for Caenorhabditis elegans foraging by covering systematically combinations of food density (across 4 orders of magnitude) and food type (across 12 bacterial strains). We found that worms' response is dominated by a single environmental variable: food density measured as number of bacteria per unit surface. They disregard other factors such as biomass content or bacterial strain. We also measured experimentally the impact on fitness of each type of food, determining that the rule is near-optimal and therefore constitutes a rule of thumb that leverages the most informative environmental variable. These results set the stage for further investigations into the underlying genetic and neural mechanisms governing this simplification process, and into its role in the evolution of decision-making strategies.

Replaying the evolution of multicellularity.

The first organisms on Earth were presumably unicellular. At one point, evolution shaped these individual cells into multicellular organisms, which was a significant transition in the history of life on Earth. To investigate how this change happened, Bozdag et al. re-ran evolution in the lab and observed how single-celled yeast forms large multicellular aggregates.

A holistic view of host-associated microbial evolution.

Microbes often live associated with other organisms. Whereas the impact of microbes on their hosts is well studied, what such a lifestyle means for the microbes is poorly understood. To address this gap, Bansept et al. explore how microbes could evolve to cope with altering between host-associated and host-free lifestyles.

Interspecies bacterial competition regulates community assembly in the C. elegans intestine.

From insects to mammals, a large variety of animals hold in their intestines complex bacterial communities that play an important role in health and disease. To further our understanding of how intestinal bacterial communities assemble and function, we study the C. elegans microbiota with a bottom-up approach by feeding this nematode with bacterial monocultures as well as mixtures of two to eight bacterial species. We find that bacteria colonizing well in monoculture do not always do well in co-cultures due to interspecies bacterial interactions. Moreover, as community diversity increases, the ability to colonize the worm gut in monoculture becomes less important than interspecies interactions for determining community assembly. To explore the role of host-microbe adaptation, we compare bacteria isolated from C. elegans intestines and non-native isolates, and we find that the success of colonization is determined more by a species' taxonomy than by the isolation source. Lastly, by comparing the assembled microbiotas in two C. elegans mutants, we find that innate immunity via the p38 MAPK pathway decreases bacterial abundances yet has little influence on microbiota composition. These results highlight that bacterial interspecies interactions, more so than host-microbe adaptation or gut environmental filtering, play a dominant role in the assembly of the C. elegans microbiota.

Transient invaders can induce shifts between alternative stable states of microbial communities.

Microbial dispersal often leads to the arrival of outsider organisms into ecosystems. When their arrival gives rise to successful invasions, outsider species establish within the resident community, which can markedly alter the ecosystem. Seemingly less influential, the potential impact of unsuccessful invaders that interact only transiently with the community has remained largely ignored. Here, we experimentally demonstrate that these transient invasions can induce a lasting transition to an alternative stable state, even when the invader species itself does not survive the transition. First, we develop a mechanistic understanding of how environmental changes caused by these transient invaders can drive a community shift in a simple, bistable model system. Beyond this, we show that transient invaders can also induce switches between stable states in more complex communities isolated from natural soil samples. Our results demonstrate that short-term interactions with an invader species can induce lasting shifts in community composition and function.

Strength of species interactions determines biodiversity and stability in microbial communities.

Organisms-especially microbes-tend to live together in ecosystems. While some of these ecosystems are very biodiverse, others are not, and while some are very stable over time, others undergo strong temporal fluctuations. Despite a long history of research and a plethora of data, it is not fully understood what determines the biodiversity and stability of ecosystems. Theory and experiments suggest a connection between species interaction, biodiversity and the stability of ecosystems, where an increase in ecosystem stability with biodiversity could be observed in several cases. However, what causes these connections remains unclear. Here, we show in microbial ecosystems in the laboratory that the concentrations of available nutrients can set the strength of interactions between bacteria. High nutrient concentrations allowed the bacteria to strongly alter the chemical environment, causing on average more negative interactions between species. These stronger interactions excluded more species from the community, resulting in a loss of biodiversity. At the same time, the stronger interactions also decreased the stability of the microbial communities, providing a mechanistic link between species interaction, biodiversity and stability in microbial ecosystems.

Conformational Dynamics of a Single Protein Monitored for 24 h at Video Rate.

We use plasmon rulers to follow the conformational dynamics of a single protein for up to 24 h at a video rate. The plasmon ruler consists of two gold nanospheres connected by a single protein linker. In our experiment, we follow the dynamics of the molecular chaperone heat shock protein 90 (Hsp90), which is known to show "open" and "closed" conformations. Our measurements confirm the previously known conformational dynamics with transition times in the second to minute time scale and reveals new dynamics on the time scale of minutes to hours. Plasmon rulers thus extend the observation bandwidth 3-4 orders of magnitude with respect to single-molecule fluorescence resonance energy transfer and enable the study of molecular dynamics with unprecedented precision.

Ecological suicide in microbes.

The growth and survival of organisms often depend on interactions between them. In many cases, these interactions are positive and caused by a cooperative modification of the environment. Examples are the cooperative breakdown of complex nutrients in microbes or the construction of elaborate architectures in social insects, in which the individual profits from the collective actions of her peers. However, organisms can similarly display negative interactions by changing the environment in ways that are detrimental for them, for example by resource depletion or the production of toxic byproducts. Here we find an extreme type of negative interactions, in which Paenibacillus sp. bacteria modify the environmental pH to such a degree that it leads to a rapid extinction of the whole population, a phenomenon that we call ecological suicide. Modification of the pH is more pronounced at higher population densities, and thus ecological suicide is more likely to occur with increasing bacterial density. Correspondingly, promoting bacterial growth can drive populations extinct whereas inhibiting bacterial growth by the addition of harmful substances-such as antibiotics-can rescue them. Moreover, ecological suicide can cause oscillatory dynamics, even in single-species populations. We found ecological suicide in a wide variety of microbes, suggesting that it could have an important role in microbial ecology and evolution.

Modifying and reacting to the environmental pH can drive bacterial interactions.

Microbes usually exist in communities consisting of myriad different but interacting species. These interactions are typically mediated through environmental modifications; microbes change the environment by taking up resources and excreting metabolites, which affects the growth of both themselves and also other microbes. We show here that the way microbes modify their environment and react to it sets the interactions within single-species populations and also between different species. A very common environmental modification is a change of the environmental pH. We find experimentally that these pH changes create feedback loops that can determine the fate of bacterial populations; they can either facilitate or inhibit growth, and in extreme cases will cause extinction of the bacterial population. Understanding how single species change the pH and react to these changes allowed us to estimate their pairwise interaction outcomes. Those interactions lead to a set of generic interaction motifs-bistability, successive growth, extended suicide, and stabilization-that may be independent of which environmental parameter is modified and thus may reoccur in different microbial systems.

Self-organized patchiness facilitates survival in a cooperatively growing Bacillus subtilis population.

Ecosystems are highly structured. Organisms are not randomly distributed but can be found in spatial aggregates at many scales, leading to spatial heterogeneity or even regular patterns(1). The widespread occurrence of these aggregates in many different ecosystems suggests that generic factors intrinsic to the populations-such as interactions between the organisms-play a major role in their emergence(1,2). Beyond the emergence of spatial patchiness, its functional consequences remain unclear. Here we show in Bacillus subtilis that cooperative interactions in a spatial environment are sufficient to form self-organized patches. These patches allow for survival even when the microbe density is too low to sustain growth in a well-mixed environment. Decreasing cell mobility leads to more compact patches that enhance this survival advantage but also reduce the overall growth. Our results highlight that even populations lacking specific group-forming mechanisms can nonetheless form spatial patterns that allow for group survival in challenging environments.

Shaping the Crowd: The Social Life of Cells.

Cells can switch between individual and collective behavior by tuning their communication.

From a ratchet mechanism to random fluctuations evolution of Hsp90's mechanochemical cycle.

The 90-kDa heat shock proteins [heat shock protein 90 (Hsp90)] are a highly conserved ATP-dependent protein family, which can be found from prokaryotic to eukaryotic organisms. In general, Hsp90s are elongated dimers with N- and C-terminal dimerization sites. In a series of publications, we have recently shown that no successive mechanochemical cycle exists for yeast Hsp90 (yHsp90) in the absence of clients or cochaperones. Here, we resolve the mechanochemical cycle of the bacterial homologue HtpG by means of two- and three-color single-molecule FRET (Förster resonance energy transfer). Unlike yHsp90, the N-terminal dynamics of HtpG is strongly influenced by nucleotide binding and turnover-its reaction cycle is driven by a mechanical ratchet mechanism. However, the C-terminal dimerization site is mainly closed and not influenced by nucleotides. The direct comparison of both proteins shows that the Hsp90 machinery has developed to a more flexible and less nucleotide-controlled system during evolution.

Heat shock protein 90's mechanochemical cycle is dominated by thermal fluctuations.

The molecular chaperone and heat shock protein 90 (Hsp90) exists mainly as a homodimer in the cytoplasm. Each monomer has an ATPase in its N-terminal domain and undergoes large conformational changes during Hsp90's mechanochemical cycle. The three-color single-molecule assay and data analysis presented in the following allows one to observe at the same time nucleotide binding and the conformational changes in Hsp90. Surprisingly, and completely unlike the prior investigated systems, nucleotides can bind to the N-terminally open and closed state without strictly forcing the protein into a specific conformation. Both the transitions between the conformational states and the nucleotide binding/unbinding are mainly thermally driven. Furthermore, the two ATP binding sites show negative cooperativity; i.e., nucleotides do not bind independently to the two monomers. We thus reveal a picture of how nucleotide binding and conformational changes are connected in the molecular chaperone Hsp90, which has far-ranging consequences for its function and is distinct from previously investigated motor proteins.

The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis.

The molecular chaperone heat-shock protein 90 (Hsp90) is one of the most abundant proteins in unstressed eukaryotic cells. Its function is dependent on an exceptionally slow ATPase reaction that involves large conformational changes. To observe these conformational changes and to understand their interplay with the ATPase function, we developed a single-molecule assay that allows examination of yeast Hsp90 dimers in real time under various nucleotide conditions. We detected conformational fluctuations between open and closed states on timescales much faster than the rate of ATP hydrolysis. The compiled distributions of dwell times allow us to assign all rate constants to a minimal kinetic model for the conformational changes of Hsp90 and to delineate the influence of ATP hydrolysis. Unexpectedly, in this model ATP lowers two energy barriers almost symmetrically, such that little directionality is introduced. Instead, stochastic, thermal fluctuations of Hsp90 are the dominating processes.