title: Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator Mutations Mediate Fitness Gains through Virulence Attenuation.
abstract: Symbiotic interactions are indispensable for metazoan function, but their origin and evolution remain elusive. We use a controlled evolution experiment to demonstrate the emergence of novel commensal interactions between Pseudomonas aeruginosa, an initially pathogenic bacterium, and a metazoan host, Caenorhabditis elegans. We show that commensalism evolves through loss of virulence, because it provides bacteria with a double fitness advantage: Increased within-host fitness and a larger host population to infect. Commensalism arises irrespective of host immune status, as the adaptive path in immunocompromised C. elegans knockouts does not differ from that in wild type. Dissection of temporal dynamics of genomic adaptation for 125 bacterial populations reveals highly parallel evolution of incipient commensalism across independent biological replicates. Adaptation is mainly achieved through frame shift mutations in the global regulator lasR and nonsynonymous point mutations in the polymerase gene rpoB that arise early in evolution. Genetic knockouts of lasR not only corroborate its role in virulence attenuation but also show that further mutations are necessary for the fully commensal phenotype. The evolutionary transition from pathogenicity to commensalism as we observe here is facilitated by mutations in global regulators such as lasR, because few genetic changes cause pleiotropic effects across the genome with large phenotypic effects. Finally, we found that nucleotide diversity increased more quickly in bacteria adapting to immunocompromised hosts than in those adapting to immunocompetent hosts. Nevertheless, the outcome of evolution was comparable across host types. Commensalism can thus evolve independently of host immune state solely as a side-effect of bacterial adaptation to novel hosts.
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany gjansen@zoologie.uni-kiel.de.
authors.forename: Gunther
authors.initials: G
authors.lastname: Jansen
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany.
authors.forename: Lena L
authors.initials: LL
authors.lastname: Crummenerl
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Gilbert
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Mohr
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany.
authors.forename: Roxana
authors.initials: R
authors.lastname: Pfefferkorn
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thänert
authors.affiliation: Molecular Cell Biology, Institute for Clinical Molecular Biology, University of Kiel, Kiel, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.affiliation: Evolutionary Ecology and Genetics, Zoological Institute, University of Kiel, Kiel, Germany.
authors.forename: Hinrich
authors.initials: H
authors.lastname: Schulenburg
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000382:microbiology*; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D056726:Genetic Association Studies; D014644:Genetic Variation; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000472:pathogenicity*; D013559:Symbiosis / Q000235:genetics; D014774:Virulence
chemical_list: D001426:Bacterial Proteins
keywords: Pseudomonas; commensalism; evolutionary transition; experimental evolution; global regulator; immunocompromised; lasR; symbiosis