title: Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes.
abstract: Bacterial pathogens evolve during the infection of their human host(1-8), but separating adaptive and neutral mutations remains challenging(9-11). Here we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple individuals. We conducted a retrospective study of a Burkholderia dolosa outbreak among subjects with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired nonsynonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes affect important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition and implicate oxygen-dependent regulation as paramount in lung infections. Several genes have not previously been implicated in pathogenesis and may represent new therapeutic targets. The identification of parallel molecular evolution as a pathogen spreads among multiple individuals points to the key selection forces it experiences within human hosts.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tami D
authors.initials: TD
authors.lastname: Lieberman
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Mythili
authors.initials: M
authors.lastname: Aingaran
authors.forename: Gail
authors.initials: G
authors.lastname: Potter-Bynoe
authors.forename: Damien
authors.initials: D
authors.lastname: Roux
authors.forename: Michael R
authors.initials: MR
authors.lastname: Davis
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.forename: Nicholas
authors.initials: N
authors.lastname: Leiby
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: McAdam
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
authors.forename: Roy
authors.initials: R
authors.lastname: Kishony
mesh_terms: D000220:Adaptation, Biological; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000382:microbiology; D019117:Burkholderia / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D019121:Burkholderia Infections / Q000453:epidemiology / Q000382:microbiology*; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D058872:Epidemics; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D016013:Likelihood Functions; D008070:Lipopolysaccharides / Q000235:genetics; D008171:Lung Diseases / Q000382:microbiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012641:Selection, Genetic; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D037521:Virulence Factors; D002939:Ciprofloxacin
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