Mostrando recursos 1 - 6 de 6

  1. A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

    Lourenço, Marta; Ramiro, Ricardo S; Güleresi, Daniela; Barroso-Batista, João; Xavier, Karina B; Gordo, Isabel; Sousa, Ana
    The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one...

  2. Macrophage adaptation leads to parallel evolution of genetically diverseEscherichia colismall-colony variants with increased fitness in vivo and antibiotic collateral sensitivity

    Ramiro, Ricardo S.; Costa, Henrique; Gordo, Isabel
    Small-colony variants (SCVs) are commonly observed in evolution experiments and clinical isolates, being associated with antibiotic resistance and persistent infections. We recently observed the repeated emergence of Escherichia coli SCVs during adaptation to the interaction with macrophages. To identify the genetic targets underlying the emergence of this clinically relevant morphotype, we performed whole-genome sequencing of independently evolved SCV clones. We uncovered novel mutational targets, not previously associated with SCVs (e.g. cydA, pepP) and observed widespread functional parallelism. All SCV clones had mutations in genes related to the electron-transport chain. As SCVs emerged during adaptation to macrophages, and often show increased...

  3. Multiple Resistance at No Cost: Rifampicin and Streptomycin a Dangerous Liaison in the Spread of Antibiotic Resistance

    Durão, Paulo; Trindade, Sandra; Sousa, Ana; Gordo, Isabel
    Evidence is mounting that epistasis is widespread among mutations. The cost of carrying two deleterious mutations, or the advantage of acquiring two beneficial alleles, is typically lower that the sum of their individual effects. Much less is known on epistasis between beneficial and deleterious mutations, even though this is key to the amount of genetic hitchhiking that may occur during evolution. This is particularly important in the context of antibiotic resistance: Most resistances are deleterious, but some can be beneficial and remarkably rifampicin resistance can emerge de novo in populations evolving without antibiotics. Here we show pervasive positive pairwise epistasis...

  4. Competition and fixation of cohorts of adaptive mutations under Fisher geometrical model

    Moura de Sousa, Jorge A.; Alpedrinha, João; Campos, Paulo R.A.; Gordo, Isabel
    One of the simplest models of adaptation to a new environment is Fisher's Geometric Model (FGM), in which populations move on a multidimensional landscape defined by the traits under selection. The predictions of this model have been found to be consistent with current observations of patterns of fitness increase in experimentally evolved populations. Recent studies investigated the dynamics of allele frequency change along adaptation of microbes to simple laboratory conditions and unveiled a dramatic pattern of competition between cohorts of mutations, i.e., multiple mutations simultaneously segregating and ultimately reaching fixation. Here, using simulations, we study the dynamics of phenotypic and...

  5. Trade-Offs of Escherichia coli Adaptation to an Intracellular Lifestyle in Macrophages

    Azevedo, M; Sousa, A; Moura de Sousa, J; Thompson, J A; Proença, J T; Gordo, I
    The bacterium Escherichia coli exhibits remarkable genomic and phenotypic variation, with some pathogenic strains having evolved to survive and even replicate in the harsh intra-macrophage environment. The rate and effects of mutations that can cause pathoadaptation are key determinants of the pace at which E. coli can colonize such niches and become pathogenic. We used experimental evolution to determine the speed and evolutionary paths undertaken by a commensal strain of E. coli when adapting to intracellular life. We estimated the acquisition of pathoadaptive mutations at a rate of 10-6 per genome per generation, resulting in the fixation of more virulent...

  6. Cognitive and Motivational Requirements for the Emergence of Cooperation in a Rat Social Game

    Viana, DS.; Gordo, I.; Sucena, E.; Moita, M.A.P.
    Background: Game theory and the Prisoner's Dilemma (PD) game in particular, which captures the paradox of cooperative interactions that lead to benefits but entail costs to the interacting individuals, have constituted a powerful tool in the study of the mechanisms of reciprocity. However, in non-human animals most tests of reciprocity in PD games have resulted in sustained defection strategies. As a consequence, it has been suggested that under such stringent conditions as the PD game humans alone have evolved the necessary cognitive abilities to engage in reciprocity, namely, numerical discrimination, memory and control of temporal discounting.

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