PLoS Biology

Journal: PLoS Biology

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PLoS biol.

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PLOS

ISSN

1544-9173
1545-7885

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Publications 1 - 10 of 103

Exploitative and Hierarchical Antagonism in a Cooperative Bacterium
Fiegna, Francesca; Velicer, Gregory J. (2005)
PLoS Biology
Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species. Such noncooperation may take the form of outright antagonism or social exploitation. Myxococcus xanthus is a highly social prokaryote that cooperatively develops into spore-bearing, multicellular fruiting bodies in response to starvation. Here we have characterized the nature of social interactions among nine developmentally proficient strains of M. xanthus isolated from spatially distant locations. Strains were competed against one another in all possible pairwise combinations during starvation-induced development. In most pairings, at least one competitor exhibited strong antagonism toward its partner and a majority of mixes showed bidirectional antagonism that decreased total spore production, even to the point of driving whole populations to extinction. Differential response to mixing was the primary determinant of competitive superiority rather than the sporulation efficiencies of unmixed populations. In some competitive pairings, the dominant partner sporulated more efficiently in mixed populations than in clonal isolation. This finding represents a novel form of exploitation in bacteria carried out by socially competent genotypes and is the first documentation of social exploitation among natural bacterial isolates. Patterns of antagonistic superiority among these strains form a highly linear dominance hierarchy. At least some competition pairs construct chimeric, rather than segregated, fruiting bodies. The cooperative prokaryote M. xanthus has diverged into a large number of distinct social types that cooperate with clone-mates but exhibit intense antagonism toward distinct social types of the same species. Most lengthy migration events in nature may thus result in strong antagonism between migratory and resident populations, and this antagonism may have large effects on local population sizes and dynamics. Intense mutual antagonism appears to be more prevalent in this prokaryotic social species than has been observed in the eukaryotic social slime mold Dictyostelium discoideum, which also exhibits multicellular development. The finding of several cases of facultative social exploitation among these natural isolates suggests that such exploitation may occur frequently in nature in many prokaryotes with cooperative traits.
Quantifying the effects of antibiotic resistance and within-host competition on strain fitness in Streptococcus pneumoniae
Krishna, Aswin; Tonkin-Hill, Gerry; Morel-Journel, Thibaut; et al. (2025)
PLoS Biology
Competition plays a key role in shaping the structure and diversity of bacterial populations. In many clinically important bacterial species, strains compete at multiple scales: at the between-host scale for new hosts to colonise, and at the within-host scale during co-colonisation. Characterising these multiple facets of competition plays an important role in understanding bacterial ecology. This is particularly relevant for antibiotic resistance, where competition between antibiotic-susceptible and resistant strains determines resistance dynamics. In this work, we perform survival analyses on a large longitudinal dataset of Streptococcus pneumoniae carriage to quantify how within-host competition affects the rates of clearance and establishment of pneumococcal strains. We find that the presence of a within-host competitor is associated with a 33% increase in clearance and a 54% reduction in establishment. Priority effects and serotype differences partially predict the outcomes of this within-host competition. Further, we quantify the effects of antibiotic resistance on between- and within-host components of fitness. Antibiotic consumption is associated with increased clearance rate for both susceptible and resistant strains, albeit to a higher extent in susceptible strains. In the absence of antibiotics, we find some evidence that resistance is associated with increased susceptibility to withinhost competition, suggesting a fitness cost of resistance. Overall, our work provides quantitative insights into pneumococcal competition across scales and the role of this competition in shaping pneumococcal epidemiology.
The IBEX Knowledge-Base: A central resource for multiplexed imaging techniques
Radtke, Andrea J.; Anidi, Ifeanyichukwu U.; Arakkal, Leanne; et al. (2025)
PLoS Biology
Multiplexed imaging is a powerful approach in spatial biology, although it is complex, expensive and labor-intensive. Here, we present the IBEX Knowledge-Base, a central resource for reagents, protocols and more, to enhance knowledge sharing, optimization and innovation of spatial proteomics techniques.
Stress-Dependent Coordination of Transcriptome and Translatome in Yeast
Halbeisen, Regula E.; Gerber, André P. (2009)
PLoS Biology
Cells rapidly alter gene expression in response to environmental stimuli such as nutrients, hormones, and drugs. During the imposed “remodeling” of gene expression, changes in the levels of particular mRNAs do not necessarily correlate with those of the encoded proteins, which could in part rely on the differential recruitment of mRNAs to translating ribosomes. To systematically address this issue, we have established an approach to rapidly access the translational status of each mRNA in the yeast Saccharomyces cerevisiae by affinity purification of endogenously formed ribosomes and the analysis of associated mRNAs with DNA microarrays. Using this method, we compared changes in total mRNA levels (transcriptome) with ribosome associations (translatome) after the application of different conditions of cellular stress. Severe stresses, induced by amino acid depletion or osmotic shock, stimulated highly correlated responses affecting about 15% of both total RNA levels and translatome. Many of the regulated messages code for functionally related proteins, thus reflecting logical responses to the particular stress. In contrast, mild stress provoked by addition of Calcofluor-white and menadione altered the translatome of approximately 1% of messages with only marginal effects on total mRNA, suggesting largely uncorrelated responses of transcriptome and translatome. Among these putative translationally regulated messages were most components of the mitochondrial ATPase. Increased polysome associations of corresponding messages and higher mitochondrial ATPase activities upon treatment confirmed the relevance for regulation of this macromolecular complex. Our results suggest the presence of highly sensitive translational regulatory networks that coordinate functionally related messages. These networks are preferentially activated for rapid adaptation of cells to minor environmental perturbations.
The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level
Jaric, Ivana; Voelkl, Bernhard; Clerc, Melanie; et al. (2022)
PLoS Biology
The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between animal facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multicentre study, whereby inbred C57BL/6J mice from a single breeding cohort were allocated to and reared in 5 different animal facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of the rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that environmental variation among animal facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organisation. We detected changes in chromatin organisation in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity, and regulation of behaviour. Our findings demonstrate that common environmental differences between animal facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and thus argue that study designs should take environmental background into account to increase the robustness and replicability of findings.
Frontostriatal pathways gate processing of behaviorally relevant reward dimensions
Weber, Susanna C.; Kahnt, Thorsten; Quednow, Boris B.; et al. (2018)
PLoS Biology
The value of rewards arises from multiple hedonic and motivational dimensions. Reward-encoding brain regions such as the ventral striatum (VS) are known to process these dimensions. However, the mechanism whereby distinct reward dimensions are selected for neural processing and guiding behavior remains unclear. Here, we used functional imaging to investigate how human individuals make either hedonic (liking) or motivational (wanting) evaluations of everyday items. We found that the two types of evaluations were differently modulated depending on whether participants won or lost these items. Neural activity in the VS encoded both hedonic and motivational dimensions of reward, whereas ventromedial prefrontal activity encoded primarily motivational evaluations and central orbitofrontal activity encoded predominantly hedonic evaluations. These distinct prefrontal representations arose regardless of which judgment was currently relevant for behavior. Critically, the VS preferentially processed the reward dimension currently being evaluated and showed judgment-specific functional connectivity with the dimension-specific prefrontal areas. Thus, our data are in line with a gating mechanism by which prefrontal cortex (PFC)–VS pathways flexibly encode reward dimensions depending on their behavioral relevance. These findings provide a prototype for a generalized information selection mechanism through content-tailored frontostriatal communication.
ANXUR Receptor-Like Kinases Coordinate Cell Wall Integrity with Growth at the Pollen Tube Tip Via NADPH Oxidases
Boisson-Dernier, Aurélien; Lituiev, Dmytro S.; Nestorova, Anna; et al. (2013)
PLoS Biology
It has become increasingly apparent that the extracellular matrix (ECM), which in plants corresponds to the cell wall, can influence intracellular activities in ways that go far beyond their supposedly passive mechanical support. In plants, growing cells use mechanisms sensing cell wall integrity to coordinate cell wall performance with the internal growth machinery to avoid growth cessation or loss of integrity. How this coordination precisely works is unknown. Previously, we reported that in the tip-growing pollen tube the ANXUR receptor-like kinases (RLKs) of the CrRLK1L subfamily are essential to sustain growth without loss of cell wall integrity in Arabidopsis. Here, we show that over-expression of the ANXUR RLKs inhibits growth by over-activating exocytosis and the over-accumulation of secreted cell wall material. Moreover, the characterization of mutations in two partially redundant pollen-expressed NADPH oxidases coupled with genetic interaction studies demonstrate that the ANXUR RLKs function upstream of these NADPH oxidases. Using the H2O2-sensitive HyPer and the Ca2+-sensitive YC3.60 sensors in NADPH oxidase-deficient mutants, we reveal that NADPH oxidases generate tip-localized, pulsating H2O2 production that functions, possibly through Ca2+ channel activation, to maintain a steady tip-focused Ca2+ gradient during growth. Our findings support a model where ECM-sensing receptors regulate reactive oxygen species production, Ca2+ homeostasis, and exocytosis to coordinate ECM-performance with the internal growth machinery.
gen3sis: A general engine for eco-evolutionary simulations of the processes that shape Earth's biodiversity
Hagen, Oskar; Fluck, Benjamin; Fopp, Fabian; et al. (2021)
PLoS Biology
Understanding the origins of biodiversity has been an aspiration since the days of early naturalists. The immense complexity of ecological, evolutionary, and spatial processes, however, has made this goal elusive to this day. Computer models serve progress in many scientific fields, but in the fields of macroecology and macroevolution, eco-evolutionary models are comparatively less developed. We present a general, spatially explicit, eco-evolutionary engine with a modular implementation that enables the modeling of multiple macroecological and macroevolutionary processes and feedbacks across representative spatiotemporally dynamic landscapes. Modeled processes can include species' abiotic tolerances, biotic interactions, dispersal, speciation, and evolution of ecological traits. Commonly observed biodiversity patterns, such as alpha, beta, and gamma diversity, species ranges, ecological traits, and phylogenies, emerge as simulations proceed. As an illustration, we examine alternative hypotheses expected to have shaped the latitudinal diversity gradient (LDG) during the Earth's Cenozoic era. Our exploratory simulations simultaneously produce multiple realistic biodiversity patterns, such as the LDG, current species richness, and range size frequencies, as well as phylogenetic metrics. The model engine is open source and available as an R package, enabling future exploration of various landscapes and biological processes, while outputs can be linked with a variety of empirical biodiversity patterns. This work represents a key toward a numeric, interdisciplinary, and mechanistic understanding of the physical and biological processes that shape Earth's biodiversity.
Resident microbial communities inhibit growth and antibiotic-resistance evolution of Escherichia coli in human gut microbiome samples
Baumgartner, Michael; Bayer, Florian; Pfrunder-Cardozo, Katia R.; et al. (2020)
PLoS Biology
Countering the rise of antibiotic-resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g., via resource competition) but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonisation by focal E. coli but also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found resistance genes, including a highly effective resistance plasmid, in resident microbial communities. We identified physical constraints on plasmid transfer that can explain why our focal strain failed to acquire some of these beneficial resistance genes, and we found some chromosomal resistance mutations were only beneficial in the absence of the resident microbiota. This suggests, depending on in situ gene transfer dynamics, interactions with resident microbiota can inhibit antibiotic-resistance evolution of individual species.
TMED2 binding restricts SMO to the ER and Golgi compartments
Di Minin, Giulio; Holzner, Markus; Grison, Alice; et al. (2022)
PLoS Biology
Hedgehog (HH) signaling is important for embryonic pattering and stem cell differentiation. The G protein–coupled receptor (GPCR) Smoothened (SMO) is the key HH signal transducer modulating both transcription-dependent and transcription-independent responses. We show that SMO protects naive mouse embryonic stem cells (ESCs) from dissociation-induced cell death. We exploited this SMO dependency to perform a genetic screen in haploid ESCs where we identify the Golgi proteins TMED2 and TMED10 as factors for SMO regulation. Super-resolution microscopy shows that SMO is normally retained in the endoplasmic reticulum (ER) and Golgi compartments, and we demonstrate that TMED2 binds to SMO, preventing localization to the plasma membrane. Mutation of TMED2 allows SMO accumulation at the plasma membrane, recapitulating early events after HH stimulation. We demonstrate the physiologic relevance of this interaction in neural differentiation, where TMED2 functions to repress HH signal strength. Identification of TMED2 as a binder and upstream regulator of SMO opens the way for unraveling the events in the ER–Golgi leading to HH signaling activation.

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