Antagonistic interactions are likely important driving forces of the evolutionary process underlying bacterial genome complexity and diversity. We hypothesized that the ability of evolved bacteria to escape specific components of host innate immunity, such as phagocytosis and killing by macrophages (MΦ), is a critical trait relevant in the acquisition of bacterial virulence. Here, we used a combination of experimental evolution, phenotypic characterization, genome sequencing and mathematical modeling to address how fast, and through how many adaptive steps, a commensal Escherichia coli (E. coli) acquire this virulence trait. We show that when maintained in vitro under the selective pressure of host MΦ commensal E. coli can evolve, in less than 500 generations, virulent clones that escape phagocytosis and MΦ killing in vitro, while increasing their pathogenicity in vivo, as assessed in mice. This pathoadaptive process is driven by a mechanism involving the insertion of a single transposable element into the promoter region of the E. coli yrfF gene. Moreover, transposition of the IS186 element into the promoter of Lon gene, encoding an ATP-dependent serine protease, is likely to accelerate this pathoadaptive process. Competition between clones carrying distinct beneficial mutations dominates the dynamics of the pathoadaptive process, as suggested from a mathematical model, which reproduces the observed experimental dynamics of E. coli evolution towards virulence. In conclusion, we reveal a molecular mechanism explaining how a specific component of host innate immunity can modulate microbial evolution towards pathogenicity.
The maintenance of diversity in the gut microbiota is a signature of host health. Yet how strain variation emerges and changes over time in this ecosystem is poorly understood.Here we use a natural yet controlled system to track the effects of natural selection by the genetic signatures it leaves in evolving populations. By following the emergence of intraspecies diversity in an Escherichia coli strain, we unravel a recurrent case of violation of Dollo's law, which proposes that evolution is unidirectional and irreversible. We demonstrate de novo acquisition of a primordial lost phenotype via compensatory mutation and also genetic reversion, the latter leaving no trace of the past. We show that this reverse evolution generates two coexisting phenotypes, resource generalist and specialist, whose abundance can be controlled by diet supplementation. While specialists' abundance is low, they avoid competition with the gut microbiota, whereas generalist abundance is dependent on microbiota composition. Our results highlight how a single genetic change can have large ecological consequences.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/096206 doi: bioRxiv preprint first posted online Dec. 22, 2016; The diversity of bacterial species inhabiting the host intestine is important for its health (1).Furthermore, within each bacterial species, many different strains can colonize the gut but the evolutionary mechanisms by which such intra-species diversity is structured remains elusive (2, 3) . In particular the dynamics of emergence and spread of adaptive mutations in commensal gut bacteria is poorly known (4). Recently using the streptomycin treated mouse model of E. coli gut colonization, and a fluorescently labeled strain, we began to uncover the nature of the adaptive process that this bacteria experiences in the gut. We found that the first steps of its adaptation, arising as rapidly as three days post-colonization, consisted in the selective inactivation of the operon that allows E. coli to metabolize galactitol (5), a sugar alcohol derived from galactose. Distinct, but phenotypically equivalent, knock out alleles of this operon bearing a similar selective effect (7.5% benefit (6)) were recurrently observed to emerge across independent populations adapting to the mouse gut (7). Thus, the distribution of fitness effects of mutations comprising the first step of adaptation to the gut could be described by a simple Dirac-Delta distribution (8). Using this experimental system, we unravel the spread of adaptive mutations, by following the dynamics of two neutral fluorescent markers in an otherwise genetically monomorphic population (5). Here, we have enquired if the pace of adaptation would slow down in the next steps of adaptation to this complex ecosystem. A deceleration in the pace of adaptation is expected under simple models of adaptation (9) and is typically found in bacterial po...
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