Antibody-mediated cross-linking of gut bacteria hinders the spread of antibiotic resistance

The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected for by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within-host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity-driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance pre-exists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within-host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine-based strategies to combat antibiotic resistance.Comment: 49 pages, 11 figure

Cultural transmission and biological markets

Active cultural transmission of fitness-enhancing behavior (sometimes called “teaching”) can be seen as a costly strategy: one for which its evolutionary stability poses a Darwinian puzzle. In this article, we offer a biological market model of cultural transmission that substitutes or complements existing kin selection-based proposals for the evolution of cultural capacities. We explicitly demonstrate how a biological market can account for the evolution of teaching when individual learners are the exclusive focus of social learning (such as in a fast-changing environment). We also show how this biological market can affect the dynamics of cumulative culture. The model works best when it is difficult to have access to the observation of the behavior without the help of the actor. However, in contrast to previous non-mathematical hypotheses for the evolution of teaching, we show how teaching evolves even when innovations are insufficiently opaque and therefore vulnerable to acquisition by emulators via inadvertent transmission. Furthermore, teaching in a biological market is an important precondition for enhancing individual learning abilitie

First evidence of anisotropic quenched disorder effects on a smectic liquid crystal confined in porous silicon

We present a neutron scattering analysis of the structure of the smectic liquid crystal octylcyanobiphenyl (8CB) confined in one-dimensional nanopores of porous silicon films (PS). The smectic transition is completely suppressed, leading to the extension of a short-range ordered smectic phase aligned along the pore axis. It evolves reversibly over an extended temperature range, down to 50 K below the \textit{N-SmA} transition in pure 8CB. This behavior strongly differs from previous observations of smectics in different one-dimensional porous materials. A coherent picture of this striking behavior requires that quenched disorder effects are invoked. The strongly disordered nature of the inner surface of PS acts as random fields coupling to the smectic order. The one-dimensionality of PS nano-channels offers new perspectives on quenched disorder effects, which observation has been restricted to homogeneous random porous materials so far.Comment: Submitted to Phys. Rev.

Multiple scales of selection influence the evolutionary emergence of novel pathogens

One contribution of 18 to a Discussion Meeting Issue 'Next-generation molecular and evolutionary epidemiology of infectious disease'. When pathogens encounter a novel environment, such as a new host species or treatment with an antimicrobial drug, their fitness may be reduced so that adaptation is necessary to avoid extinction. Evolutionary emergence is the process by which new pathogen strains arise in response to such selective pressures. Theoretical studies over the last decade have clarified some determinants of emergence risk, but have neglected the influence of fitness on evolutionary rates and have not accounted for the multiple scales at which pathogens must compete successfully. We present a cross-scale theory for evolutionary emergence, which embeds a mechanistic model of withinhost selection into a stochastic model for emergence at the population scale. We explore how fitness landscapes at within-host and between-host scales can interact to influence the probability that a pathogen lineage will emerge successfully. Results show that positive correlations between fitnesses across scales can greatly facilitate emergence, while cross-scale conflicts in selection can lead to evolutionary dead ends. The local genotype space of the initial strain of a pathogen can have disproportionate influence on emergence probability. Our cross-scale model represents a step towards integrating laboratory experiments with field surveillance data to create a rational framework to assess emergence risk

Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA

The restriction endonuclease EcoRV can rapidly locate a short recognition site within long non-cognate DNA using ‘facilitated diffusion’. This process has long been attributed to a sliding mechanism, in which the enzyme first binds to the DNA via nonspecific interaction and then moves along the DNA by 1D diffusion. Recent studies, however, provided evidence that 3D translocations (hopping/jumping) also help EcoRV to locate its target site. Here we report the first direct observation of sliding and jumping of individual EcoRV molecules along nonspecific DNA. Using fluorescence microscopy, we could distinguish between a slow 1D diffusion of the enzyme and a fast translocation mechanism that was demonstrated to stem from 3D jumps. Salt effects on both sliding and jumping were investigated, and we developed numerical simulations to account for both the jump frequency and the jump length distribution. We deduced from our study the 1D diffusion coefficient of EcoRV, and we estimated the number of jumps occurring during an interaction event with nonspecific DNA. Our results substantiate that sliding alternates with hopping/jumping during the facilitated diffusion of EcoRV and, furthermore, set up a framework for the investigation of target site location by other DNA-binding proteins

Cultural transmission and biological markets

Active cultural transmission of fitness-enhancing behavior (sometimes called “teaching”) can be seen as a costly strategy: one for which its evolutionary stability poses a Darwinian puzzle. In this article, we offer a biological market model of cultural transmission that substitutes or complements existing kin selection-based proposals for the evolution of cultural capacities. We explicitly demonstrate how a biological market can account for the evolution of teaching when individual learners are the exclusive focus of social learning (such as in a fast-changing environment). We also show how this biological market can affect the dynamics of cumulative culture. The model works best when it is difficult to have access to the observation of the behavior without the help of the actor. However, in contrast to previous non-mathematical hypotheses for the evolution of teaching, we show how teaching evolves even when innovations are insufficiently opaque and therefore vulnerable to acquisition by emulators via inadvertent transmission. Furthermore, teaching in a biological market is an important precondition for enhancing individual learning abilitie

Stratégies de recherche optimales et marches aléatoires intermittentes : de l'enzyme de restriction au vol de l'albatros

long résumé en français, texte principal en anglais.This thesis deals with intermittent target search strategies, which combine slow phases, allowing the searcher to detect the target, and fast phases without detection. Foraging animals are an example at the macroscopic scale. We propose a model, alternative to the famous Lévy strategies, and show analytically that the mean search time can be minimized as a function of the mean duration of both phases. Our first example at the microscopic scale is given by proteins searching for targets on DNA. We analytically calculate the distribution of the distance travelled along DNA during a 3D excursion, adapt it to a single-molecule experiment and show that the observed trajectories combine 1D and 3D diffusion. Another cellular example is provided by active transport of vesicles, which diffuse or bind to motors performing ballistic motion.We optimize the global kinetic constant within a general framework of reactions limited by this kind of transport. Finally, these intermittent strategies could constitute a generic search mechanism. We systematically study the influence both of the modeling of the detection phase and of the space dimension, and show that the optimality of intermittent strategies is a robust result.Cette thèse concerne les stratégies de recherches de cible dites intermittentes, qui alternent des phases lentes permettant la détection de la cible, et des phases rapides sans détection. Un exemple à l'échelle macroscopique est celui d'animaux en quête de nourriture. Nous en proposons un modèle, alternatif aux célèbres stratégies de Lévy, et montrons analytiquement que le temps moyen de recherche peut être minimisé en fonction des durées moyennes de chaque phase. Un premier exemple à l'échelle microscopique est celui de la recherche par des protéines de cibles sur l'ADN. Nous calculons analytiquement la distribution de la distance parcourue le long de l'ADN lors d'une excursion 3D, l'adaptons à une expérience de molécule unique et montrons que les trajectoires observées combinent des diffusions 1D et 3D. Un autre exemple cellulaire concerne le transport actif de vésicules, qui diffusent ou se lient à des moteurs assurant un déplacement balistique. Nous optimisons la constante cinétique dans un modèle général de réaction limitée par ce type de transport. Finalement, ces stratégies intermittentes pourraient constituer un mécanisme de recherche générique. Nous étudions de manière systématique l'influence de la modélisation de la phase de détection et de la dimension de l'espace, et montrons que l'optimalité des stratégies intermittentes est un résultat robuste

Cultural transmission and biological markets

Active cultural transmission of fitness-enhancing behavior (sometimes called ¿teaching¿) can be seen as a costly strategy: one for which its evolutionary stability poses a Darwinian puzzle. In this article, we offer a biological market model of cultural transmission that substitutes or complements existing kin selection-based proposals for the evolution of cultural capacities. We demonstrate how a biological market can account for the evolution of teaching when individual learners are the exclusive focus of social learning (such as in a fast-changing environment). We also show how this biological market can affect the dynamics of cumulative culture. The model works best when it is difficult to have access to the observation of the behavior without the help of the actor. However, in contrast to previous non-mathematical hypotheses for the evolution of teaching, we show how teaching evolves, even when innovations are insufficiently opaque and therefore vulnerable to acquisition by emulators via inadvertent transmission. Furthermore, teaching in a biological market is an important precondition for enhancing individual learning abilities

Optimal search strategies and intermittent random walks (from restriction enzymes to albatros flights)

Cette thèse concerne les stratégies de recherches de cible dites intermittentes, qui alternent des phases lentes permettant la détection de la cible, et des phases rapides sans détection. Un exemple à l'échelle macroscopique est celui d'animaux en quête de nourriture. Nous en proposons un modèle, alternatif aux célèbres stratégies de Lévy, et montrons analytiquement que le temps moyen de recherche peut être minimisé en fonction des durées moyennes de chaque phase. Un premier exemple à l'échelle microscopique est celui de la recherche par des protéines de cibles sur l'ADN. Nous calculons analytiquement la distribution de la distance parcourue le long de l'ADN lors d'une excursion 3D, l'adaptons à une expérience de molécule unique et montrons que les trajectoires observées combinent des diffusions 1D et 3D. Un autre exemple cellulaire concerne le transport actif de vésicules, qui diffusent ou se lient à des moteurs assurant un déplacement balistique. Nous optimisons la constante cinétique dans un modèle général de réaction limitée par ce type de transport. Finalement, ces stratégies intermittentes pourraient constituer un mécanisme de recherche générique. Nous étudions de manière systématique l'influence de la modélisation de la phase de détection et de la dimension de l'espace, et montrons que l'optimalité des stratégies intermittentes est un résultat robuste.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF