Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

Coevolution of dispersal in a parasitoid-host system

Interspecific interactions and the evolution of dispersal are both of interest when considering the potential impact of habitat fragmentation on community ecology, but the interaction between these processes is not well studied. We address this by considering the coevolution of dispersal strategies in a host-parasitoid system. An individual-based host-parasitoid metapopulation model was constructed for a patchy environment, allowing for evolution in dispersal rates of both species. Highly rarefied environments with few suitable patches selected against dispersal in both species, as did relatively static environments. Provided that parasitoids persist, all parameter values studied led to stable equilibria in dispersal rates for both species. There was a tendency towards higher dispersal rates in parasitoids due to the asymmetric relationships of the two species to the patches: vacant patches are most valuable for hosts, but unsuitable for parasitoids, which require an established host population to reproduce. High host dispersal rate was favoured by high host population growth rate, and in the parasitoid by high growth rates in both species

Poly(I:C) Enhances the Susceptibility of Leukemic Cells to NK Cell Cytotoxicity and Phagocytosis by DC

α Active specific immunotherapy aims at stimulating the host's immune system to recognize and eradicate malignant cells. The concomitant activation of dendritic cells (DC) and natural killer (NK) cells is an attractive modality for immune-based therapies. Inducing immunogenic cell death to facilitate tumor cell recognition and phagocytosis by neighbouring immune cells is of utmost importance for guiding the outcome of the immune response. We previously reported that acute myeloid leukemic (AML) cells in response to electroporation with the synthetic dsRNA analogue poly(I:C) exert improved immunogenicity, demonstrated by enhanced DC-activating and NK cell interferon-γ-inducing capacities. To further invigorate the potential of these immunogenic tumor cells, we explored their effect on the phagocytic and cytotoxic capacity of DC and NK cells, respectively. Using single-cell analysis, we assessed these functionalities in two- and three-party cocultures. Following poly(I:C) electroporation AML cells become highly susceptible to NK cell-mediated killing and phagocytosis by DC. Moreover, the enhanced killing and the improved uptake are strongly correlated. Interestingly, tumor cell killing, but not phagocytosis, is further enhanced in three-party cocultures provided that these tumor cells were upfront electroporated with poly(I:C). Altogether, poly(I:C)-electroporated AML cells potently activate DC and NK cell functions and stimulate NK-DC cross-talk in terms of tumor cell killing. These data strongly support the use of poly(I:C) as a cancer vaccine component, providing a way to overcome immune evasion by leukemic cells

The History of Makassan Trepang Fishing and Trade

The Malayan term trepang describes a variety of edible holothurians commonly known as sea cucumbers. Although found in temperate and tropical marine waters all over the world, the centre of species diversity and abundance are the shallow coastal waters of Island Southeast Asia. For at least 300 years, trepang has been a highly priced commodity in the Chinese market. Originally, its fishing and trade was a specialized business, centred on the town of Makassar in South Sulawesi (Indonesia). The rise of trepang fishing in the 17th century added valuable export merchandize to the rich shallow seas surrounding the islands of Southeast Asia. This enabled local communities to become part of large trading networks and greatly supported their economic development. In this article, we follow Makassan trepang fishing and trading from its beginning until the industrialization of the fishery and worldwide depletion of sea cucumbers in the 20th century. Thereby, we identify a number of characteristics which trepang fishing shares with the exploitation of other marine resources, including (1) a strong influence of international markets, (2) the role of patron-client relationships which heavily influence the resource selection, and (3) the roving-bandit-syndrome, where fishermen exploit local stocks of valuable resources until they are depleted, and then move to another area. We suggest that understanding the similarities and differences between historical and recent exploitation of marine resources is an important step towards effective management solutions

Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor

<div><p>Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.</p></div

Metabolic and demographic feedbacks shape the emergent spatial structure and function of microbial communities

Microbes are predominantly found in surface-attached and spatially structured polymicrobial communities. Within these communities, microbial cells excrete a wide range of metabolites, setting the stage for interspecific metabolic interactions. The links, however, between metabolic and ecological interactions (functional relationships), and species spatial organization (structural relationships) are still poorly understood. Here, we use an individual-based modelling framework to simulate the growth of a two-species surface-attached community where food (resource) is traded for detoxification (service) and investigate how metabolic constraints of individual species shape the emergent structural and functional relationships of the community. We show that strong metabolic interdependence drives the emergence of mutualism, robust interspecific mixing, and increased community productivity. Specifically, we observed a striking and highly stable emergent lineage branching pattern, generating a persistent lineage mixing that was absent when the metabolic exchange was removed. These emergent community properties are driven by demographic feedbacks, such that aid from neighbouring cells directly enhances focal cell growth, which in turn feeds back to neighbour fecundity. In contrast, weak metabolic interdependence drives conflict (exploitation or competition), and in turn greater interspecific segregation. Together, these results support the idea that species structural and functional relationships represent the net balance of metabolic interdependencies

Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a Contact- and IL-15-Dependent Manner

<div><p>The contribution of natural killer (NK) cells to the treatment efficacy of dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much current efforts to optimize this form of immunotherapy are therefore geared towards harnessing the NK cell-stimulatory ability of DCs. In this study, we investigated whether generation of human monocyte-derived DCs with interleukin (IL)-15 followed by activation with a Toll-like receptor stimulus endows these DCs, commonly referred to as “IL-15 DCs”, with the capacity to stimulate NK cells. In a head-to-head comparison with “IL-4 DCs” used routinely for clinical studies, IL-15 DCs were found to induce a more activated, cytotoxic effector phenotype in NK cells, in particular in the CD56^bright NK cell subset. With the exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK-resistant targets. This effect was found to require cell-to-cell contact and to be mediated by DC surface-bound IL-15. This study shows that DCs can express a membrane-bound form of IL-15 through which they enhance NK cell cytotoxic function. The observed lack of membrane-bound IL-15 on “gold-standard” IL-4 DCs and their consequent inability to effectively promote NK cell cytotoxicity may have important implications for the future design of DC-based cancer vaccine studies.</p></div