What have we learned about microbiomes in 2021?
A scientific year in review:
Live imaging of bacteria that kill their rivals with phage weapons
Phage tail-like bacteriocins – or tailocins – are proteins produced by bacteria to puncture the membranes of rival cells and hence eliminate them. In natural microbiomes, tailocins could play the role of narrow-spectrum weapons used by bacteria against related strains with which they compete for resources. In January, a study from the group of Christoph Keel (University of Lausanne) offered an unprecedented visual exploration of the production, release and killing activity of bacterial tailocins at the microscopic scale. This experimental set-up revealed how bacterial cells, using a controlled explosive lysis, eject tailocins beyond their immediate vicinity, potentially reaching many target competitors in their microenvironment. The authors suggest that tailocins may be tailored weapons used by bacteria to weaken their direct ecological competitors while leaving other potentially beneficial microbes unscathed.
Uncovering prophages in gut bacteria using metagenomic data
Bacteriophages affect the abundance and diversity of bacterial populations in all environments, including the human gut – with consequences for our health. Many phages reside as a latent DNA sequence within the bacterial chromosome (a ‘prophage’), until induced to replicate and form new active viral particles. Such phages are notoriously difficult to find and study, however, a new method now permits the use of high-throughput sequencing data to map inducible prophages in the genome of their host and quantify their activity in the microbiome. Published in March, this study is a close collaboration between the groups of Wolf-Dietrich Hardt and Shini Sunagawa (both at ETH Zurich).
In search of the soil microbial interactome: exploration of bacterial interactions in microbeads
Bacterial interactions assays often rely on culturable isolates and experiments on agar plates. In April, the team of Jan van der Meer (University of Lausanne) published a new approach using thousands of agarose minibeads that embed single cells or pairs of bacterial cells isolated from a natural soil. Using quantitative imaging, the study measured microbial growth in the microbeads, revealing a counterintuitive result: some mixed pairs of cells grew more productively than single cells, highlighting positive interactions among soil microbes. However, while certain pairs led to synergistic growth, the authors also observed many negative outcomes; mathematical models suggested that negative interactions became more dominant in the confined and less connected environment of the beads. (Read the ‘Behind the paper’ article)
Vaccines that lure Salmonella bacteria into an evolutionary trap
Developing effective vaccines against bacteria in the gut is challenging, as bacterial pathogens manage to escape the immune response by changing their outer surface antigens. But this microbial ability to vary can be exploited against the pathogens, as brilliantly demonstrated by the teams of Emma Slack (ETH Zurich), Wolf-Dietrich Hardt (ETH Zurich), and Médéric Diard (University of Basel). Published in May, the study resulting from this collaboration detailed how the researchers carefully designed a combination vaccine against Salmonella bacteria in the mouse gut. This oral vaccine created a selection pressure that drove Salmonella towards a specific type of mutation to evade immunity – a mutation that also rendered them more susceptible to stress and predation by phages. As a result, the bacteria became unable to infect gut tissues and cause disease. This new vaccine proved more efficient at preventing infection that currently approved vaccines in pigs and chickens, opening up exciting new venues for such evolutionary vaccines in veterinary and human medicine. (Read the ETH News article)
Microbes participate to a general immune training in plants
In May and June, two new studies from the team of Julia Vorholt (ETH Zurich), in collaboration with the team of Shini Sunagawa (ETH Zurich), brought to light some fascinating aspects of the plant-microbe dialogue. In the first study, Arabidopsis plants that grew under sterile conditions were exposed to selected leaf bacterial isolates, followed by transcriptomics and metabolomics analyses. Researchers subsequently discovered a central molecular response of the plant, named the general non-self response, which involves 24 core plant genes key to plant defense against pathogens. A second study examined how Arabidopsis mutants with a defective immune system would differ in their leaf microbiome compared to a wild-type plant. The largest observed effects in microbiome composition resulted from a mutation in an NADPH oxidase gene. Knockout plants for the oxidase enzyme were enriched in some bacteria, such as Xanthomonas, that acted as opportunistic pathogens within the new genetic make-up of the host. The plant immune system is thus essential to microbiome homeostasis, just as the microbiome is needed to train a healthy plant immune response. (Read the ETH News article)
Food partitioning facilitates the coexistence of bacteria in the gut
In the gut of animals, many related bacterial species can coexist despite having similar metabolisms, hence eschewing the pressure of competition. How do they achieve this? In July, the team of Philipp Engel (University of Lausanne), in collaboration with the group of Uwe Sauer (ETH Zurich and NCCR Antiresist), demonstrated in a study that dietary resource partitioning could account for the maintenance of species diversity in the gut. Working with honey bees colonized with a defined mix of related bacterial species, they showed in vivo and in vitro that gut coexistence was possible when the bees were fed with pollen (a complex mix of sugars and proteins), while a diet of simple sugar led to competitive exclusion. Metatranscriptomics and metabolomics analyses brought further insights into the coexistence mechanisms: while the species had closely related genomes, they activated different sets of genes in the bee gut and as a result consumed different sets of metabolites, or consumed the same metabolites at different rates. Complementary and overlapping feeding profiles thus sustain bacterial coexistence in the bee gut. (Read the Insight article)
Microbial life in a crowded habitat: computing the key role of space and diffusion
At the microscale, the metabolic activity of microbes and their cell-to-cell interactions are in part controlled by nutrients diffusion. However, in many natural microbial communities, the close proximity between microbial cells and the presence of extracellular polymeric substances typically impede the free diffusion of nutrients and metabolites. To realistically model such crowded habitats, the team of Vassily Hatzimanikatis (EPFL) has developed CROMICS, a spatio-temporal framework that combines individual-based modeling, scaled particle theory, and thermodynamic flux analysis. CROMICS thus integrates the metabolic capabilities, the size, and the location of each individual cell, as well as the distribution of metabolites, in the medium. Metabolic interactions among cells then arise naturally through competition for or the exchange of metabolites. Published in July, joint studies presented the new modelling framework and investigated its relevance in biofilm simulations. The developed framework holds great promise for future studies of host-microbiome metabolic interactions.
Major advances in taxonomic profiling from shotgun sequencing data
Classifying sequence reads and quantifying the relative abundance of taxa in a community is a hallmark of microbiome research. The team of Shini Sunagawa (ETH Zurich) has developed new softwares and databases that offer unparalleled capabilities for metagenomic and metatranscriptomic profiling, published over July and August. First, mOTUs is a profiling tool with an extended database of marker genes obtained from diverse environments, which allows for quantification of known as well as currently unknown prokaryotic species. (mOTUs ranked first in an independent benchmark of profiling tools.) Moreover, the mTAGs tool enables the analysis of 16S rRNA gene fragments directly from shotgun data, using degenerate consensus reference sequences of ribosomal RNA genes. Both mOTUs and mTAGs are freely available to the research community.
A single-cell perspective sheds new light on Salmonella infections
To cause infections in humans, Salmonella bacteria rely on a subset of cells that provoke gut inflammation, while the other Salmonella cells take advantage and proliferate. Short-chain fatty acids secreted by the human gut microbiome are known to reduce the proportion of the inflammatory cell type, however, the mechanism is unclear. In a study published in August, the team of Martin Ackermmann (ETH Zurich), working in collaboration with Wolf-Dietrich Hardt (ETH Zurich), used microfluidics and time-lapse microscopy to show that SCFAs selectively reduce the growth of the inflammatory bacteria compared to the rest of the population. (Read the ‘Behind the paper’ article)
Bacterial degradation of marine snow is coupled with water flow
In the upper level of the ocean, microscopic algae use photosynthesis to capture CO2 and grow. When they die, they trickle down to the bottom of the ocean as ‘marine snow’. The amount of carbon that is ultimately transported to the seafloor by this route depends on the rate of degradation of this snow by marine bacteria. Published in September, a study by the group of Roman Stocker (ETH Zurich) used organic particles exposed to bacteria in microfluidic chambers to demonstrate that even modest water flows enhance the particle degradation rate by more than ten-fold compared to still water. In the ocean, this means that the sinking of marine snow to the seafloor, which creates water flow around the particles, speeds up its biodegradation by bacteria. Further mathematical modelling suggests that this process could reduce by half the theoretical carbon transport efficiency in the ocean. (read the ETH News article)
Congratulations to all NCCR PhD students, postdocs and scientific staff authors: Liliana Angeles-Martinez, Markus Arnoldini, Miriam Bortfeld-Miller, Benjamin Daniel, Alyson Hockenberry, Patrick Kiefer, Alessio Milanese, François Peaudecerf, Andrew Quinn, Hans Ruscheweyh, Guillem Salazar, Martin Schäfer, Anna Sintsova, Jordan Vacheron.