Timing of Pathogen Adaptation to a Multicomponent Treatment

The sustainable use of multicomponent treatments such as combination therapies, combination vaccines/chemicals, and plants carrying multigenic resistance requires an understanding of how their population-wide deployment affects the speed of the pathogen adaptation. Here, we develop a stochastic model describing the emergence of a mutant pathogen and its dynamics in a heterogeneous host population split into various types by the management strategy. Based on a multi-type Markov birth and death process, the model can be used to provide a basic understanding of how the life-cycle parameters of the pathogen population, and the controllable parameters of a management strategy affect the speed at which a pathogen adapts to a multicomponent treatment. Our results reveal the importance of coupling stochastic mutation and migration processes, and illustrate how their stochasticity can alter our view of the principles of managing pathogen adaptive dynamics at the population level. In particular, we identify the growth and migration rates that allow pathogens to adapt to a multicomponent treatment even if it is deployed on only small proportions of the host. In contrast to the accepted view, our model suggests that treatment durability should not systematically be identified with mutation cost. We show also that associating a multicomponent treatment with defeated monocomponent treatments can be more durable than associating it with intermediate treatments including only some of the components. We conclude that the explicit modelling of stochastic processes underlying evolutionary dynamics could help to elucidate the principles of the sustainable use of multicomponent treatments in population-wide management strategies intended to impede the evolution of harmful populations.Comment: 3 figure

Sustainable deployment of QTLs conferring quantitative resistance to crops: first lessons from a stochastic model

Quantitative plant disease resistance is believed to be more durable than qualitative resistance, since it exerts less selective pressure on the pathogens. However, the process of progressive pathogen adaptation to quantitative resistance is poorly understood, which makes it difficult to predict its durability or to derive principles for its sustainable deployment. Here, we study the dynamics of pathogen adaptation in response to quantitative plant resistance affecting pathogen reproduction rate and its carrying capacity. We developed a stochastic model for the continuous evolution of a pathogen population within a quantitatively resistant host. We assumed that pathogen can adapt to a host by the progressive restoration of reproduction rate or of carrying capacity, or of both. Our model suggests that a combination of QTLs affecting distinct pathogen traits was more durable if the evolution of repressed traits was antagonistic. Otherwise, quantitative resistance that depressed only pathogen reproduction was more durable. In order to decelerate the progressive pathogen adaptation, QTLs that decrease the pathogen's ability to extend must be combined with QTLs that decrease the spore production per lesion or the infection efficiency or that increase the latent period. Our theoretical framework can help breeders to develop principles for sustainable deployment of quantitative trait loci.

Exponentiality of first passage times of continuous time Markov chains

Let (X,\p_x) be a continuous time Markov chain with finite or countable state space $S$ and let $T$ be its first passage time in a subset $D$ of $S$. It is well known that if $\mu$ is a quasi-stationary distribution relatively to $T$, then this time is exponentially distributed under \p_\mu. However, quasi-stationarity is not a necessary condition. In this paper, we determine more general conditions on an initial distribution $\mu$ for $T$ to be exponentially distributed under \p_\mu. We show in addition how quasi-stationary distributions can be expressed in terms of any initial law which makes the distribution of $T$ exponential. We also study two examples in branching processes where exponentiality does imply quasi-stationarity

The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge

La remise en cause du tracé du projet Tangentielle Ouest phase 2 lors de l’enquête publique

The challenging of the “Tangentielle Ouest phase 2” project layout during public inquiry by one of the main founders is a new situation for STIF, transport planner in Ile-de-France. The risks for the project are technical, financial, legal but also calendar. So, the project owner has to study this demand and find a technical solution in order to permit a project advance. This report deals also with the technical information exchanged by actors on the challenging of the layout.La remise en cause d’un projet en phase d’enquête publique par l’un des financeurs est un événement inédit au STIF, maître d’ouvrage coordonnateur, qui n’a jamais été confronté à une telle demande et doit donc fournir une réponse technique et juridique adaptée.Ce rapport présente la problématique de demande de révision du tracé intervenue en cours d’enquête publique sur le projet émanant de l’un des principaux financeurs et les moyens mis en œuvre par la maîtrise d’ouvrage pour y répondre. Le consensus formé sur le tracé présenté à l’enquête publique et ses signes de fragilité seront tout d’abord présentés, puis il sera procédé à l’étude des arguments techniques échangés par les différents acteurs. Enfin, nous nous concentrerons sur les méthodes utilisées par l’ingénieur pour réduire les risques financiers, techniques, administratifs et relatifs au calendrier du projet. Ce travail inédit à ce stade d’un projet au STIF permet de mettre en lumière la réponse technique du maître d’ouvrage à une telle demande

Emergence time as a function of the mutation cost.

<p>The emergence time is plotted for a two-component treatment (, green, left axis) and a three-component treatment (, red, right axis) at low (solid line) and high (dotted line) migration rates. (A) The management strategy splits the host population into a 1∶1 mixture of untreated and multicomponent-treatment receiving hosts (Str5, Fig. 2A). (B) Multicomponent treatment is deployed with other treatments involving different combinations of the components, so that the host type carrying the muticomponent treatment constitutes 50% of the host population, and the other host types are present in equal proportions (Str2, Fig. 2A). In (A) and (B), we let , , , and . In all simulations the initial population size of the resident pathogen type is , and for all , .</p

Definition of variables and parameters used to model pathogen adaptive dynamics.

<p>Definition of variables and parameters used to model pathogen adaptive dynamics.</p

Thermo-Regulated Adhesion of the Streptococcus thermophilus Delta rgg0182 Strain

International audienceThe physicochemical determinants governing the temperature-dependent adhesion of Streptococcus thermophilus to abiotic surfaces are identified under physiological condition for cells either lacking or not the Rgg(0182) transcriptional regulator involved in their thermal adaptation. For that purpose, the wild type LMG18311 strain and Delta rgg(0182) mutant were imaged using highly resolved atomic force microscopy (AFM) at various cell growth temperatures (42 to 55 degrees C). The corresponding hydrophobic/hydrophilic balance of the cells was quantitatively addressed via the measurement by chemical force microcopy of their adhesion to a reference hydrophobic surface. Analysis of force-separation distance curves further allowed us to discriminate cell surfaces according to the presence or absence of biopolymers. These results were interpreted in relation to the measured adhesion of the Delta rgg(0182) mutant onto the hydrophobic wall of microwells in the temperature range from 46 to 52 degrees C. It is evidenced that the viscoelastic Delta rgg(0182) cell envelop behaves as a thermo-responsive film whose hydrophobicity increases with increasing temperature, thereby favoring cell attachment to hydrophobic surfaces. Regardless cell growth temperature, wild-type cells do not attach to hydrophobic surfaces and the presence of the Rgg(0182) transcriptional regulator is associated with the synthesis of hydrophilic cell surface biopolymers. Throughout, the impact of electrostatics on bioadhesion is ruled out upon examination of electrohydrodynamic cell properties at 50 degrees C

Impact of cell surface molecules on conjugative transfer of the integrative and conjugative element ICESt3 of Streptococcus thermophilus

International audienceIntegrative Conjugative Elements (ICEs) are chromosomal elements that are widely distributed in bacterial genomes, hence contributing to genome plasticity, adaptation and evolution of bacteria. Conjugation requires a contact between both the donor and the recipient cells and thus likely depends on the composition of the cell surface envelope. In this work, we investigated the impact of different cell surface molecules including cell surface proteins, wall teichoic acids, lipoteichoic acids and exopolysaccharides on the transfer and acquisition of ICESt3 from Streptococcus thermophilus The transfer of ICESt3 from wild type donor towards mutated recipient cells increased 5- to 400-fold compared to WT when recipients cells were affected in lipoproteins, teichoic acids or exopolysaccharides. These mutants displayed an increased biofilm-forming ability compared to WT suggesting better cell interactions that could contribute to the increase of ICESt3 acquisition. Microscopic observations of S. thermophilus cell surface mutants showed different phenotypes (aggregation in particular) that can also have an impact on conjugation.By contrast, the same mutations did not have the same impact when the donor cells, instead of recipient cells, were mutated. In that case, the transfer frequency of ICESt3 decreased compared to WT. The same observation was made when both donor and recipient cells were mutated. The dominant effect of mutations in donor suggests that modifications of the cell envelope could impair the establishment or activity of the conjugation machinery required for DNA transport. IMPORTANCE: ICEs contribute to horizontal gene transfer of adaptive traits (for example virulence, antibiotic resistance or biofilm formation) and play a considerable role in bacterial genome evolution thus underlying the need of a better understanding of their conjugative mechanism of transfer. While most studies are focusing on the different functions encoded by ICEs, little is known about the effect of host factors on their conjugative transfer. Using ICESt3 of S. thermophilus as a model of study, we demonstrated the impact of lipoproteins, teichoic acids and exopolysaccharides on ICE transfer and acquisition. This opens up new avenues to control gene transfers mediated by ICEs