title: Trade-Offs of Escherichia coli Adaptation to an Intracellular Lifestyle in Macrophages.
abstract: 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 strains in less than a hundred generations. Whole genome sequencing of independently evolved clones showed that the main targets of intracellular adaptation involved loss of function mutations in genes implicated in the assembly of the lipopolysaccharide core, iron metabolism and di- and tri-peptide transport, namely rfaI, fhuA and tppB, respectively. We found a substantial amount of antagonistic pleiotropy in evolved populations, as well as metabolic trade-offs, commonly found in intracellular bacteria with reduced genome sizes. Overall, the low levels of clonal interference detected indicate that the first steps of the transition of a commensal E. coli into intracellular pathogens are dominated by a few pathoadaptive mutations with very strong effects.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande n°6, Oeiras, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Azevedo
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande n°6, Oeiras, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Sousa
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande n°6, Oeiras, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Moura de Sousa
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande n°6, Oeiras, Portugal.
authors.forename: J A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande n°6, Oeiras, Portugal.
authors.forename: J T
authors.initials: JT
authors.lastname: Proença
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande n°6, Oeiras, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Gordo
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000818:Animals; D005075:Biological Evolution; D002999:Clone Cells; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D056084:Genetic Fitness; D056426:Genetic Loci; D005947:Glucose / Q000494:pharmacology; D006239:Haplotypes; D042541:Intracellular Space / Q000382:microbiology*; D007501:Iron / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D008320:Maltose / Q000494:pharmacology; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D000067996:RAW 264.7 Cells
chemical_list: D029968:Escherichia coli Proteins; D008320:Maltose; D007501:Iron; D005947:Glucose