65 research outputs found
Synergy and Group Size in Microbial Cooperation
No full textMicrobes produce many molecules that are important for their growth and development, and the exploitation of these secretions by nonproducers has recently become an important paradigm in microbial social evolution. Although the production of these public-goods molecules has been studied intensely, little is known of how the benefits accrued and the costs incurred depend on the quantity of public-goods molecules produced. We focus here on the relationship between the shape of the benefit curve and cellular density, using a model assuming three types of benefit functions: diminishing, accelerating, and sigmoidal (accelerating and then diminishing). We classify the latter two as being synergistic and argue that sigmoidal curves are common in microbial systems. Synergistic benefit curves interact with group sizes to give very different expected evolutionary dynamics. In particular, we show that whether and to what extent microbes evolve to produce public goods depends strongly on group size. We show that synergy can create an "evolutionary trap" that can stymie the establishment and maintenance of cooperation. By allowing density-dependent regulation of production (quorum sensing), we show how this trap may be avoided. We discuss the implications of our results on experimental design.</p
Erratic Flu Vaccination Emerges from Short-Sighted Behavior in Contact Networks
No full textDaniel M. Cornforth is with UT Austin, Timothy C. Reluga is with Pennsylvania State University, Eunha Shim is with Yale University School of Medicine, Chris T. Bauch is with University of Guelph, Alison P. Galvani is with Yale University School of Medicine, Lauren Ancel Meyers is with UT Austin and the Santa Fe Institute.The effectiveness of seasonal influenza vaccination programs depends on individual-level compliance. Perceptions about risks associated with infection and vaccination can strongly influence vaccination decisions and thus the ultimate course of an epidemic. Here we investigate the interplay between contact patterns, influenza-related behavior, and disease dynamics by incorporating game theory into network models. When individuals make decisions based on past epidemics, we find that individuals with many contacts vaccinate, whereas individuals with few contacts do not. However, the threshold number of contacts above which to vaccinate is highly dependent on the overall network structure of the population and has the potential to oscillate more wildly than has been observed empirically. When we increase the number of prior seasons that individuals recall when making vaccination decisions, behavior and thus disease dynamics become less variable. For some networks, we also find that higher flu transmission rates may, counterintuitively, lead to lower (vaccine-mediated) disease prevalence. Our work demonstrates that rich and complex dynamics can result from the interaction between infectious diseases, human contact patterns, and behavior.This research was supported by NIH grant U01 GM087719, grants from the James F. McDonnell Foundation and Bill and Stephanie Sick to LAM, and the Bill and Melinda Gates Foundation grant 49276 to TCR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o
Group size dependent benefits in microbe cooperation
No full textMicrobes produce many molecules that are important for their growth and development, and the production and exploitation of these public goods has become an important paradigm in the field of microbial social evolution. Here I explore this type of microbial sociality in two primary chapters. In the first chapter I focus on the relationship between the shape of the benefit curve and cellular density with a model assuming three types of benefit functions: diminishing, accelerating, and sigmoidal (accelerating then diminishing). I classify the latter two as being synergistic and argue that sigmoidal curves are common in microbial systems. Synergistic benefit curves interact with group sizes to give very different expected evolutionary dynamics. In particular, whether or not and to what extent microbes evolve to produce public goods depends strongly on group size. This synergy can create an ``evolutionary trap'' which can stymie the establishment and maintenance of cooperation. By allowing density dependent regulation of production (quorum sensing), this trap may be avoided. In the second chapter I focus again on group size benefits, but with a particular focus on pathogen risk assessment. Many pathogens are thought to behave collectively, and yet the models used in assessing microbial risk assume otherwise. In particular the dominant paradigm, articulated in the Independent Action Hypothesis, is that infecting microorganisms do not interact with each other and that each cell has an independent likelihood of causing infection. Initial data from a bacteria-insect system suggest that indeed the Independent Action Hypothesis may be incorrect and leads to poor risk assessment at low doses. I argue that more attention to mechanisms of infection is essential for accurate risk assessment
Competition sensing: the social side of bacterial stress responses.
No full textThe field of ecology has long recognized two types of competition: exploitative competition, which occurs indirectly through resource consumption, and interference competition, whereby one individual directly harms another. Here, we argue that these two forms of competition have played a dominant role in the evolution of bacterial regulatory networks. In particular, we argue that several of the major bacterial stress responses detect ecological competition by sensing nutrient limitation (exploitative competition) or direct cell damage (interference competition). We call this competition sensing: a physiological response that detects harm caused by other cells and that evolved, at least in part, for that purpose. A key prediction of our hypothesis is that bacteria will counter-attack when they sense ecological competition but not when they sense abiotic stress. In support of this hypothesis, we show that bacteriocins and antibiotics are frequently upregulated by stress responses to nutrient limitation and cell damage but very rarely upregulated by stress responses to heat or osmotic stress, which typically are not competition related. We argue that stress responses, in combination with the various mechanisms that sense secretions, enable bacteria to infer the presence of ecological competition and navigate the 'microbe-kill-microbe' world in which they live
Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control
No full textStandard virulence evolution theory assumes that virulence factors are maintained because they aid parasitic exploitation, increasing growth within and/or transmission between hosts. An increasing number of studies now demonstrate that many opportunistic pathogens (OPs) do not conform to these assumptions, with virulence factors maintained instead because of advantages in non-parasitic contexts. Here we review virulence evolution theory in the context of OPs and highlight the importance of incorporating environments outside a focal virulence site. We illustrate that virulence selection is constrained by correlations between these external and focal settings and pinpoint drivers of key environmental correlations, with a focus on generalist strategies and phenotypic plasticity. We end with a summary of key theoretical and empirical challenges to be met for a fuller understanding of OPs.</p
Relative proximity of chromosome territories influences chromosome exchange partners in radiation-induced chromosome rearrangements in primary human bronchial epithelial cells
No full textCopyright © 2013 The Authors. This article is made available through the Brunel Open Access Publishing Fund. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.Copyright © 2013 The Authors. It is well established that chromosomes exist in discrete territories (CTs) in interphase and are positioned in a cell-type specific probabilistic manner. The relative localisation of individual CTs within cell nuclei remains poorly understood, yet many cancers are associated with specific chromosome rearrangements and there is good evidence that relative territorial position influences their frequency of exchange. To examine this further, we characterised the complexity of radiation-induced chromosome exchanges in normal human bronchial epithelial (NHBE) cells by M-FISH analysis of PCC spreads and correlated the exchanges induced with their preferred interphase position, as determined by 1/2-colour 2D-FISH analysis, at the time of irradiation. We found that the frequency and complexity of aberrations induced were reduced in ellipsoid NHBE cells in comparison to previous observations in spherical cells, consistent with aberration complexity being dependent upon the number and proximity of damaged CTs, i.e. lesion proximity. To ask if particular chromosome neighbourhoods could be identified we analysed all radiation-induced pair-wise exchanges using SCHIP (statistics for chromosome interphase positioning) and found that exchanges between chromosomes (1;13), (9;17), (9;18), (12;18) and (16;21) all occurred more often than expected assuming randomness. All of these pairs were also found to be either sharing similar preferred positions in interphase and/or sharing neighbouring territory boundaries. We also analysed a human small cell lung cancer cell line, DMS53, by M-FISH observing the genome to be highly rearranged, yet possessing rearrangements also involving chromosomes (1;13) and (9;17). Our findings show evidence for the occurrence of non-random exchanges that may reflect the territorial organisation of chromosomes in interphase at time of damage and highlight the importance of cellular geometry for the induction of aberrations of varying complexity after exposure to both low and high-LET radiation.Department of Healt
Data from: Bacterial cooperation causes systematic errors in pathogen risk assessment due to the failure of the independent action hypothesis
No full textThe Independent Action Hypothesis (IAH) states that pathogenic individuals (cells, spores, virus particles etc.) behave independently of each other, so that each has an independent probability of causing systemic infection or death. The IAH is not just of basic scientific interest; it forms the basis of our current estimates of infectious disease risk in humans. Despite the important role of the IAH in managing disease interventions for food and water-borne pathogens, experimental support for the IAH in bacterial pathogens is indirect at best. Moreover since the IAH was first proposed, cooperative behaviors have been discovered in a wide range of microorganisms, including many pathogens. A fundamental principle of cooperation is that the fitness of individuals is affected by the presence and behaviors of others, which is contrary to the assumption of independent action. In this paper, we test the IAH in Bacillus thuringiensis (B.t), a widely occurring insect pathogen that releases toxins that benefit others in the inoculum, infecting the diamondback moth, Plutella xylostella. By experimentally separating B.t. spores from their toxins, we demonstrate that the IAH fails because there is an interaction between toxin and spore effects on mortality, where the toxin effect is synergistic and cannot be accommodated by independence assumptions. Finally, we show that applying recommended IAH dose-response models to high dose data leads to systematic overestimation of mortality risks at low doses, due to the presence of synergistic pathogen interactions. Our results show that cooperative secretions can easily invalidate the IAH, and that such mechanistic details should be incorporated into pathogen risk analysis.Cornforth, Daniel M.; Matthews, Andrew; Brown, Sam P.; Raymond, Ben (2016). Data from: Bacterial cooperation causes systematic errors in pathogen risk assessment due to the failure of the independent action hypothesis [Dataset]. Dryad. https://doi.org/10.5061/dryad.72f4
Enkele verwaarloosde organisatorische vraagstukken van de Interregionale Rechercheteams (IRT's)
No full textGroup size dependent benefits in microbe cooperation
No full textMicrobes produce many molecules that are important for their growth and development, and the production and exploitation of these public goods has become an important paradigm in the field of microbial social evolution. Here I explore this type of microbial sociality in two primary chapters.
In the first chapter I focus on the relationship between the shape of the benefit curve and cellular density with a model assuming three types of benefit functions: diminishing, accelerating, and sigmoidal (accelerating then diminishing). I classify the latter two as being synergistic and argue that sigmoidal curves are common in microbial systems. Synergistic benefit curves interact with group sizes to give very different expected evolutionary dynamics. In particular, whether or not and to what extent microbes evolve to produce public goods depends strongly on group size. This synergy can create an ``evolutionary trap'' which can stymie the establishment and maintenance of cooperation. By allowing density dependent regulation of production (quorum sensing), this trap may be avoided.
In the second chapter I focus again on group size benefits, but with a particular focus on
pathogen risk assessment. Many pathogens are thought to behave collectively, and yet the models used in assessing microbial risk assume otherwise. In particular the dominant paradigm, articulated in the Independent Action Hypothesis, is that infecting microorganisms do not interact with each other and that each cell has an independent likelihood of causing infection. Initial data from a bacteria-insect system suggest that indeed the Independent Action Hypothesis may be incorrect and leads to poor risk assessment at low doses. I argue that more attention to mechanisms of infection is essential for accurate risk assessment.This thesis is not currently available in ORA
- …
