http://hdl.handle.net/10400.7/5 2020-03-07T13:41:59Z 2020-03-07T13:41:59Z Sousa, Ana Ramiro, Ricardo S. Barroso-Batista, João Güleresi, Daniela Lourenço, Marta Gordo, Isabel http://hdl.handle.net/10400.7/873 2018-11-01T01:30:09Z 2017-11-01T00:00:00Z

Título: Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria Autor: Sousa, Ana; Ramiro, Ricardo S.; Barroso-Batista, João; Güleresi, Daniela; Lourenço, Marta; Gordo, Isabel Resumo: The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut. Descrição: The deposited article is a post-print version and has been submitted to peer review.; This deposit is composed by the main article plus the supplementary materials of the publication.

2017-11-01T00:00:00Z Sousa, Ana Frazão, Nelson Ramiro, Ricardo S Gordo, Isabel http://hdl.handle.net/10400.7/872 2018-08-01T00:30:08Z 2017-08-01T00:00:00Z

Título: Evolution of commensal bacteria in the intestinal tract of mice Autor: Sousa, Ana; Frazão, Nelson; Ramiro, Ricardo S; Gordo, Isabel Resumo: Hundreds of different bacterial species inhabit our intestines and contribute to our health status, with significant loss of species diversity typically observed in disease conditions. Within each microbial species a great deal of diversity is hidden and such intra-specific variation is also key to the proper homeostasis between the host and its microbial inhabitants. Indeed, it is at this level that new mechanisms of antibiotic resistance emerge and pathogenic characteristics evolve. Yet, our knowledge on intra-species variation in the gut is still limited and an understanding of the evolutionary mechanisms acting on it is extremely reduced. Here we review recent work that has begun to reveal that adaptation of commensal bacteria to the mammalian intestine may be fast and highly repeatable, and that the time scales of evolutionary and ecological change can be very similar in these ecosystems. Descrição: The deposited article is a post-print version and has been submitted to peer review.; This deposit is composed by the main article, and it hasn't any supplementary materials associated.; This publication hasn't any creative commons license associated.

2017-08-01T00:00:00Z Durão, Paulo Gülereşi, Daniela Proença, João Gordo, Isabel http://hdl.handle.net/10400.7/871 2018-05-19T02:00:32Z 2016-09-01T00:00:00Z

Título: Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages Autor: Durão, Paulo; Gülereşi, Daniela; Proença, João; Gordo, Isabel Resumo: The evolution of multiple-antibiotic-resistant bacteria is an increasing global problem. Even though mutations causing resistance usually incur a fitness cost in the absence of antibiotics, the magnitude of such costs varies across environments and genomic backgrounds. We studied how the combination of mutations that confer resistance to rifampin (Rif(r)) and streptomycin (Str(r)) affects the fitness of Escherichia coli when it interacts with cells from the immune system, i.e., macrophages (Mϕs). We found that 13 Rif(r) Str(r) doubly resistant genotypes, of the 16 tested, show a survival advantage inside Mϕs, indicating that double resistance can be highly beneficial in this environment. Our results suggest that there are multiple paths to acquire multiple-drug resistance in this context, i.e., if a clone carrying Rif(r) allele H526 or S531 acquires a second mutation conferring Str(r), the resulting double mutant has a high probability of showing increased survival inside Mϕs. On the other hand, we found two cases of sign epistasis between mutations, leading to a significant decrease in bacterial survival. Remarkably, infection of Mϕs with one of these combinations, K88R+H526Y, resulted in an altered pattern of gene expression in the infected Mϕs. This indicates that the fitness effects of resistance may depend on the pattern of gene expression of infected host cells. Notwithstanding the benefits of resistance found inside Mϕs, the Rif(r) Str(r) mutants have massive fitness costs when the bacteria divide outside Mϕs, indicating that the maintenance of double resistance may depend on the time spent within and outside phagocytic cells. Descrição: The deposited article is a post-print version and has been submitted to peer review.; This deposit is composed by the main article plus the supplementary materials of the publication.

2016-09-01T00:00:00Z Moura de Sousa, Jorge Sousa, Ana Bourgard, Catarina Gordo, Isabel http://hdl.handle.net/10400.7/870 2018-05-19T02:00:21Z 2015-09-01T00:00:00Z

Título: Potential for adaptation overrides cost of resistance Autor: Moura de Sousa, Jorge; Sousa, Ana; Bourgard, Catarina; Gordo, Isabel Resumo: To investigate the cost of antibiotic resistance versus the potential for resistant clones to adapt in maintaining polymorphism for resistance. Materials & methods: Experimental evolution of Escherichia coli carrying different resistance alleles was performed under an environment devoid of antibiotics and evolutionary parameters estimated from their frequencies along time. Results & conclusion: Costly resistance mutations were found to coexist with lower cost resistances for hundreds of generations, contrary to the hypothesis that the cost of a resistance dictates its extinction. Estimated evolutionary parameters for the different resistance backgrounds suggest a higher adaptive potential of clones with costly antibiotic resistance mutations, overriding their initial cost of resistance and allowing their maintenance in the absence of drugs. Descrição: The deposited article is a post-print version and has been submitted to peer review.; This deposit is composed by the main article plus the supplementary materials of the publication.; This work is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

2015-09-01T00:00:00Z Proença, João T. Barral, Duarte C. Gordo, Isabel http://hdl.handle.net/10400.7/774 2017-07-13T02:00:32Z 2017-07-03T00:00:00Z

Título: Commensal-to-pathogen transition: One-single transposon insertion results in two pathoadaptive traits in Escherichia coli -macrophage interaction Autor: Proença, João T.; Barral, Duarte C.; Gordo, Isabel Resumo: Escherichia coli is both a harmless commensal in the intestines of many mammals, as well as a dangerous pathogen. The evolutionary paths taken by strains of this species in the commensal-to-pathogen transition are complex and can involve changes both in the core genome, as well in the pan-genome. One way to understand the likely paths that a commensal strain of E. coli takes when evolving pathogenicity is through experimentally evolving the strain under the selective pressures that it will have to withstand as a pathogen. Here, we report that a commensal strain, under continuous pressure from macrophages, recurrently acquired a transposable element insertion, which resulted in two key phenotypic changes: increased intracellular survival, through the delay of phagosome maturation and increased ability to escape macrophages. We further show that the acquisition of the pathoadaptive traits was accompanied by small but significant changes in the transcriptome of macrophages upon infection. These results show that under constant pressures from a key component of the host immune system, namely macrophage phagocytosis, commensal E. coli rapidly acquires pathoadaptive mutations that cause transcriptome changes associated to the host-microbe duet. Descrição: There are no funders and sponsors indicated explicitly in the document. This deposit is composed by the main article plus the supplementary materials of the publication.

2017-07-03T00:00:00Z