Microbial adaptation within ecosystems

Funder

Organizational Unit

Publications

The first steps of adaptation of Escherichia coli to the gut are dominated by soft sweeps

Publication . João Barroso-Batista; Ana Sousa; Marta Lourenço; Marie-Louise Bergman; Jocelyne Demengeot; Karina B. Xavier; Isabel Gordo

The accumulation of adaptive mutations is essential for survival in novel environments. However, in clonal populations with a high mutational supply, the power of natural selection is expected to be limited. This is due to clonal interference - the competition of clones carrying different beneficial mutations - which leads to the loss of many small effect mutations and fixation of large effect ones. If interference is abundant, then mechanisms for horizontal transfer of genes, which allow the immediate combination of beneficial alleles in a single background, are expected to evolve. However, the relevance of interference in natural complex environments, such as the gut, is poorly known. To address this issue, we studied the invasion of beneficial mutations responsible for Escherichia coli's adaptation to the mouse gut and demonstrate the pervasiveness of clonal interference. The observed dynamics of change in frequency of beneficial mutations are consistent with soft sweeps, where a similar adaptive mutation arises repeatedly on different haplotypes without reaching fixation. The genetic basis of the adaptive mutations revealed a striking parallelism in independently evolving populations. This was mainly characterized by the insertion of transposable elements in both coding and regulatory regions of a few genes. Interestingly in most populations, we observed a complete phenotypic sweep without loss of genetic variation. The intense clonal interference during adaptation to the gut environment, here demonstrated, may be important for our understanding of the levels of strain diversity of E. coli inhabiting the human gut microbiota and of its recombination rate.

2014-03-06Journal article

Open access

Natural Genome Diversity of AI-2 Quorum Sensing in Escherichia coli: Conserved Signal Production but Labile Signal Reception

Publication . Brito, P. H.; Rocha, E. P. C.; Xavier, K. B.; Gordo, I.

Quorum sensing (QS) regulates the onset of bacterial social responses in function to cell density having an important impact in virulence. Autoinducer-2 (AI-2) is a signal that has the peculiarity of mediating both intra- and interspecies bacterial QS. We analyzed the diversity of all components of AI-2 QS across 44 complete genomes of Escherichia coli and Shigella strains. We used phylogenetic tools to study its evolution and determined the phenotypes of single-deletion mutants to predict phenotypes of natural strains. Our analysis revealed many likely adaptive polymorphisms both in gene content and in nucleotide sequence. We show that all natural strains possess the signal emitter (the luxS gene), but many lack a functional signal receptor (complete lsr operon) and the ability to regulate extracellular signal concentrations. This result is in striking contrast with the canonical species-specific QS systems where one often finds orphan receptors, without a cognate synthase, but not orphan emitters. Our analysis indicates that selection actively maintains a balanced polymorphism for the presence/absence of a functional lsr operon suggesting diversifying selection on the regulation of signal accumulation and recognition. These results can be explained either by niche-specific adaptation or by selection for a coercive behavior where signal-blind emitters benefit from forcing other individuals in the population to haste in cooperative behaviors.

2012-12-10Journal article

Open access

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

Publication . 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 genetic change as asexual populations under clonal interference climb a Fisherian landscape, and ask about the conditions under which FGM can display the simultaneous increase and fixation of multiple mutations-mutation cohorts-along the adaptive walk. We find that FGM under clonal interference, and with varying levels of pleiotropy, can reproduce the experimentally observed competition between different cohorts of mutations, some of which have a high probability of fixation along the adaptive walk. Overall, our results show that the surprising dynamics of mutation cohorts recently observed during experimental adaptation of microbial populations can be expected under one of the oldest and simplest theoretical models of adaptation-FGM.

2016-08-02Journal article

Open access

Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

Publication . Miskinyte, M.; Gordo, I.

Mutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the rpoB, rpsL, and gyrA genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits-growth rate and survival ability-of 12 Escherichia coli K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all E. coli streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of E. coli in the context of an infection.

2013-01Journal article

Open access

An ABC Method for Estimating the Rate and Distribution of Effects of Beneficial Mutations

Publication . Moura de Sousa, J. A.; Campos, P. R. A.; Gordo, I.

Determining the distribution of adaptive mutations available to natural selection is a difficult task. These are rare events and most of them are lost by chance. Some theoretical works propose that the distribution of newly arising beneficial mutations should be close to exponential. Empirical data are scarce and do not always support an exponential distribution. Analysis of the dynamics of adaptation in asexual populations of microorganisms has revealed that these can be summarized by two effective parameters, the effective mutation rate, Ue, and the effective selection coefficient of a beneficial mutation, Se. Here, we show that these effective parameters will not always reflect the rate and mean effect of beneficial mutations, especially when the distribution of arising mutations has high variance, and the mutation rate is high. We propose a method to estimate the distribution of arising beneficial mutations, which is motivated by a common experimental setup. The method, which we call One Biallelic Marker Approximate Bayesian Computation, makes use of experimental data consisting of periodic measures of neutral marker frequencies and mean population fitness. Using simulations, we find that this method allows the discrimination of the shape of the distribution of arising mutations and that it provides reasonable estimates of their rates and mean effects in ranges of the parameter space that may be of biological relevance.

2013-03-23Journal article

Open access