scholarly journals Refined quantification of infection bottlenecks and pathogen dissemination with STAMPR

2021 ◽  
Author(s):  
Karthik Hullahalli ◽  
Justin R. Pritchard ◽  
Matthew K. Waldor
Keyword(s):  
Population Dynamics ◽  
Allelic Diversity ◽  
Systemic Infection ◽  
Pathogen Population ◽  
Founding Population ◽  
Population Sizes ◽  
Microbe Interactions ◽  
Microbial Population Dynamics ◽  
Host Microbe Interactions ◽  
Using Data

AbstractPathogen population dynamics during infection are critical determinants of infection susceptibility and define patterns of dissemination. However, deciphering pathogen population dynamics, particularly founding population sizes in host organs and patterns of dissemination between organs, is difficult due to the fact that measuring bacterial burden alone is insufficient to observe these patterns. Introduction of allelic diversity into otherwise identical bacteria using DNA barcodes enables sequencing-based measurements of these parameters, in a method known as STAMP (Sequence Tag-Based analysis of Microbial Population dynamics). However, bacteria often undergo unequal expansion within host organs, resulting in marked differences in the frequencies of barcodes in input and output libraries. Here, we show that these differences confound STAMP-based analyses of founding population sizes and dissemination patterns. We present STAMPR, a successor to STAMP that accounts for such population expansions. Using data from systemic infection of barcoded Extraintestinal Pathogenic E. coli we show that this new framework along with the metrics it yields enhances the fidelity of measurements of bottlenecks and dissemination patterns. STAMPR was also validated on an independent, barcoded Pseudomonas aeruginosa dataset, uncovering new patterns of dissemination within the data. This framework (available at https://github.com/hullahalli/stampr_rtisan), when coupled with barcoded datasets, enables a more complete assessment of within-host bacterial population dynamics.ImportanceBarcoded bacteria are often employed to monitor pathogen population dynamics during infection. The accuracy of these measurements is diminished by unequal bacterial expansion rates. Here, we develop computational tools to circumvent this limitation and establish additional metrics that collectively enhance the fidelity of measuring within-host pathogen founding population sizes and dissemination patterns. These new tools will benefit future studies of the dynamics of pathogens and symbionts within their respective hosts, and may have additional barcode-based applications beyond host-microbe interactions.

scholarly journals Fungal microbiomes are determined by host phylogeny and exhibit widespread associations with the bacterial microbiome

2021 ◽  
Vol 288 (1957) ◽  
pp. 20210552
Author(s):  
Xavier A. Harrison ◽  
Allan D. McDevitt ◽  
Jenny C. Dunn ◽  
Sarah M. Griffiths ◽  
Chiara Benvenuto ◽  
...  
Keyword(s):  
Bacterial Communities ◽  
Natural Populations ◽  
Sample Type ◽  
Fungal Community Composition ◽  
Tissue Storage ◽  
Bacterial Microbiome ◽  
Host Phylogeny ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Using Data

Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, we present novel evidence of strong covariation between fungal and bacterial communities across the host phylogeny, indicative of recruitment by hosts for specific suites of microbes. Using co-occurrence networks, we demonstrate marked variation across host taxonomy in patterns of covariation between bacterial and fungal abundances. Host phylogeny drives differences in the overall richness of bacterial and fungal communities, but the effect of diet on richness was only evident in the mammalian gut microbiome. Sample type, tissue storage and DNA extraction method also affected bacterial and fungal community composition, and future studies would benefit from standardized approaches to sample processing. Collectively these data indicate fungal microbiomes may play a key role in host fitness and suggest an urgent need to study multiple agents of the animal microbiome to accurately determine the strength and ecological significance of host–microbe interactions.

scholarly journals Integrative developmental ecology: a review of density-dependent effects on life-history traits and host-microbe interactions in non-social holometabolous insects

2020 ◽  
Vol 34 (5) ◽  
pp. 659-680 ◽  
Author(s):  
Anh The Than ◽  
Fleur Ponton ◽  
Juliano Morimoto
Keyword(s):  
Population Dynamics ◽  
Life History ◽  
Life History Traits ◽  
Larval Density ◽  
Future Research ◽  
Density Dependent ◽  
Integrative Framework ◽  
Wide Range ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Abstract Population density modulates a wide range of eco-evolutionary processes including inter- and intra-specific competition, fitness and population dynamics. In holometabolous insects, the larval stage is particularly susceptible to density-dependent effects because the larva is the resource-acquiring stage. Larval density-dependent effects can modulate the expression of life-history traits not only in the larval and adult stages but also downstream for population dynamics and evolution. Better understanding the scope and generality of density-dependent effects on life-history traits of current and future generations can provide useful knowledge for both theory and experiments in developmental ecology. Here, we review the literature on larval density-dependent effects on fitness of non-social holometabolous insects. First, we provide a functional definition of density to navigate the terminology in the literature. We then classify the biological levels upon which larval density-dependent effects can be observed followed by a review of the literature produced over the past decades across major non-social holometabolous groups. Next, we argue that host-microbe interactions are yet an overlooked biological level susceptible to density-dependent effects and propose a conceptual model to explain how density-dependent effects on host-microbe interactions can modulate density-dependent fitness curves. In summary, this review provides an integrative framework of density-dependent effects across biological levels which can be used to guide future research in the field of ecology and evolution.

scholarly journals Muc2 mucin limits Listeria monocytogenes dissemination and modulates its population dynamics

2020 ◽  
Author(s):  
Ting Zhang ◽  
Jumpei Sasabe ◽  
Brandon Sit ◽  
Matthew K. Waldor
Keyword(s):  
Population Dynamics ◽  
Listeria Monocytogenes ◽  
Intestinal Tract ◽  
Systemic Disease ◽  
Major Constituent ◽  
Infection Model ◽  
Wild Type ◽  
Founding Population ◽  
Systemic Dissemination ◽  
Population Sizes

AbstractThe mucin Muc2 is a major constituent of the mucus layer that covers the intestinal epithelium and creates a barrier between epithelial cells and luminal commensal or pathogenic microorganisms. The Gram-positive food-borne pathogen Listeria monocytogenes can cause enteritis and also disseminate from the intestine to give rise to systemic disease. L. monocytogenes can bind to intestinal Muc2, but the influence of the Muc2 mucin barrier on L. monocytogenes intestinal colonization and systemic dissemination has not been explored. Here, we used an orogastric L. monocytogenes infection model to investigate the role of Muc2 in host defense against L. monocytogenes. Compared to wild-type mice, we found that Muc2-/- mice exhibited heightened susceptibility to orogastric challenge with L. monocytogenes, with higher mortality, elevated colonic pathology, and increased pathogen burdens in both the intestinal tract and distal organs. In contrast, L. monocytogenes burdens were equivalent in wild-type and Muc2-/- animals when the pathogen was administered intraperitoneally, suggesting that systemic immune defects do not explain the heightened pathogen dissemination observed with oral infection route. Using a barcoded L. monocytogenes library to measure intra-host pathogen population dynamics, we found that Muc2-/- animals had larger pathogen founding population sizes in the intestine and distal sites than observed in wild-type animals. Comparisons of barcode frequencies revealed that, in the absence of Muc2, the colon becomes the major source for seeding the internal organs. Together, our findings reveal that Muc2 limits L. monocytogenes dissemination from the intestinal tract and modulates its population dynamics during infection.

scholarly journals Making the invisible visible: exploring host–microbiome interactions across different taxa using data-driven 3D visualization

2021 ◽  
Author(s):  
Susanne H. Landis ◽  
Tom Duscher ◽  
Thomas C.G. Bosch
Keyword(s):  
3D Visualization ◽  
Interactive Media ◽  
Visual Communication Design ◽  
Microbiome Research ◽  
Scientific Poster ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions ◽  
Using Data ◽  
User Friendly

The importance of microbiome research is rapidly gaining momentum for understanding its role in development, evolution, ecology, health and disease. Recent progress in community and single-cell genomic approaches has provided an unprecedented amount of information on the abundance and ecology of microbes in different host organisms and turned them into metaorganisms. A metaorganism is a host and its complete microbial community which is commonly referred to as the microbiome. Over half the cells in a human body are not human but belong to the multitude of species that compose our microbiome. However, linkages between metaorganisms from different taxa and their in situ level of intraspecific dependence (be it growth, division or metabolic activity) are much more scarce. Visualization therefore is crucial for understanding host–microbe interactions as well as overarching concepts in different host organisms. Here we introduce an innovative user-friendly method for interactive visualization of microbiome multi-omics data. The new communication format combines science and visual communication design. Interactive media are used to transform scientific findings on host–microbe interactions in an intuitive way. The method provides access to additional layers of information that cannot be visualized using a traditional platform. We demonstrate the usefulness of this visualization approach using the interactive scientific poster ‘Digital Meta’, which is designed to support not only interdisciplinary co-working but also communication with the general public.

scholarly journals Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of α-1 antitrypsin

2011 ◽  
Vol 434 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Louise Meinert Niclasen ◽  
Johan G. Olsen ◽  
Robert Dagil ◽  
Zhang Qing ◽  
Ole E. Sørensen ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Systemic Infection ◽  
Contact System ◽  
Bacterial Survival ◽  
Bacterial Killing ◽  
Additional Layer ◽  
Streptococcal Pyrogenic Exotoxin B ◽  
Microbe Interactions ◽  
System Activation ◽  
Host Microbe Interactions

The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after systemic spreading. Addition of SpeB to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and modification of the serpin A1AT (α-1 antitrypsin). Consequently, addition of A1AT to plasma increased bacterial survival. Sequestration of A1AT by SpeB led to enhanced contact system activation, supported by increased bacterial growth in prekallikrein deficient plasma. In a mouse model of systemic infection, administration of SpeB reduced significantly bacterial dissemination. The findings reveal an additional layer of complexity to host–microbe interactions that may be of benefit in the treatment of severe bacterial infections.

scholarly journals Glycan-Based Shaping Of The Microbiota During Primate Evolution

2021 ◽  
Author(s):  
Sumnima Singh ◽  
Patricia Bastos-Amador ◽  
Jessica A. Thompson ◽  
Mauro Truglio ◽  
Bahtiyar Yilmaz ◽  
...  
Keyword(s):  
Selection Pressure ◽  
Bacterial Species ◽  
Systemic Infection ◽  
Primate Evolution ◽  
Severe Form ◽  
Loss Of Function ◽  
Genes Encoding ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
High Selection

AbstractGenes encoding certain glycosyltransferases are thought to be under relatively high selection pressure, due to the involvement of the glycans that they synthesize in host-microbe interactions. Here we used a mouse model to investigate whether the loss of α-1,3-galactosyltransferase (GGTA1) function and Galα1-3Galβ1-4GlcNAcβ1-R (αGal) expression during primate evolution might have affected host-microbiota interactions. We found that Ggta1 deletion in mice shaped the composition of the gut microbiota in relation to the bacterial species present. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with IgA targeting of αGal-expressing bacteria. Systemic infection by the Ig-shaped microbiota elicited a less severe form of sepsis than infection with the non-Ig-shaped microbiota. This suggests that in the absence of host αGal, the microbiota is shaped towards lower pathogenicity, likely providing a fitness gain to the host. We infer that high selection pressure exerted by bacterial sepsis may have contributed to increase frequency of GGTA1 loss-of-function mutations in ancestral primates that gave rise to humans.

scholarly journals The population dynamics of a bacterial pathogen after host re-infection affects the founding population size

2016 ◽  
Author(s):  
Gaofei Jiang ◽  
Rémi Peyraud ◽  
Philippe Remigi ◽  
Alice Guidot ◽  
Richard Berthomé ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Population Size ◽  
Bacterial Pathogen ◽  
Priority Effects ◽  
Multiple Infections ◽  
Global Changes ◽  
Founder Population ◽  
Effective Population ◽  
Pathogen Population ◽  
Founding Population

AbstractIn natura, many organisms face multiple infections by pathogens. The ability of a pathogen to reinfect an already-infected host affects the genetic makeup of the pathogen population at the end of the infectious cycle. Despite the likely prevalence of this situation, the population dynamics of pathogens during multiple infections over time is still poorly understood. Here we combined theoretical and empirical investigations of the founding population size, a critical driver of the evolution of pathogens, in a setting allowing for multiple and subsequent re-infections. Using the soil-borne bacterial pathogen Ralstonia solanacearum and tomato as its host, we first assessed the strength of the host infection bottleneck, and showed that both the host barrier and the immune system work additively to constrain the infection. Then, by increasing the temperature, we experimentally demonstrated that the increased pathogen proliferation within the host reduces the contribution of subsequent re-infection leading to a lower founding population size. Our study highlights the importance of within-host pathogen proliferation in determining founding population size – and thus bacterial genetic diversity during epidemics – for pathosystems where multiple re-infections occur. Under current global changes, our work notably predicts that an increased temperature provided this increase has a beneficial impact on pathogen growth, should decrease the founding population size and as a consequence potentially lower the diversity of the infecting and transmitted pathogen population.Significance StatementFounder population size is a major determinant of pathogen evolution, yet we still have limited insights into effective populations in natural settings. Most studies have considered infection as a single event, followed by pathogen growth in the host. But, in natura, organisms typically face multiple infections by several co-exisiting pathogen strains. Therefore, effective population size will depend on the timing and relative growth rate of the different infecting strains. In this work, we predict and experimentally show that both priority effects and within-host competition determines effective founding size, with an over-contribution of fast-growing and early infecting genotypes. This work sheds a new light on the ecological and evolutionary pressures affecting infection dynamics in realistic conditions.

scholarly journals Glycan-based shaping of the microbiota during primate evolution

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sumnima Singh ◽  
Patricia Bastos-Amador ◽  
Jessica Ann Thompson ◽  
Mauro Truglio ◽  
Bahtiyar Yilmaz ◽  
...  
Keyword(s):  
Systemic Infection ◽  
Primate Evolution ◽  
Severe Form ◽  
Loss Of Function ◽  
Bacterial Sepsis ◽  
Genes Encoding ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
High Selection ◽  
Dependent Mechanism

Genes encoding glycosyltransferases can be under relatively high selection pressure, likely due to the involvement of the glycans synthesized in host-microbe interactions. Here, we used mice as an experimental model system to investigate whether loss of α−1,3-galactosyltransferase gene (GGTA1) function and Galα1-3Galβ1-4GlcNAcβ1-R (αGal) glycan expression affects host-microbiota interactions, as might have occurred during primate evolution. We found that Ggta1 deletion shaped the composition of the gut microbiota. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with targeting of αGal-expressing bacteria by IgA. Systemic infection with an Ig-shaped microbiota inoculum elicited a less severe form of sepsis compared to infection with non-Ig-shaped microbiota. This suggests that in the absence of host αGal, antibodies can shape the microbiota towards lower pathogenicity. Given the fitness cost imposed by bacterial sepsis, we infer that the observed reduction in microbiota pathogenicity upon Ggta1 deletion in mice may have contributed to increase the frequency of GGTA1 loss-of-function mutations in ancestral primates that gave rise to humans.

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