Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes

• Published in: Nature genetics Vol. 43; no. 12; pp. 1275 - 1280
• Main Authors: Lieberman, Tami D, Michel, Jean-Baptiste, Aingaran, Mythili, Potter-Bynoe, Gail, Roux, Damien, Davis, Michael R, Skurnik, David, Leiby, Nicholas, LiPuma, John J, Goldberg, Joanna B, McAdam, Alexander J, Priebe, Gregory P, Kishony, Roy
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2011; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/208/514/1948; 631/326/41/2531; Adaptation, Biological; Agriculture; Animal Genetics and Genomics; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Bacteremia - microbiology; Bacteria; Bacterial genetics; Bacterial infections; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Burkholderia; Burkholderia - drug effects; Burkholderia - genetics; Burkholderia - pathogenicity; Burkholderia Infections - epidemiology; Burkholderia Infections - microbiology; Cancer Research; Ciprofloxacin - pharmacology; Cloning; Cystic fibrosis; Drug Resistance, Bacterial; Epidemics; Evolution; Evolution & development; Evolution, Molecular; Evolutionary biology; Fundamental and applied biological sciences. Psychology; Gene Function; Genes, Bacterial; Genetic aspects; Genetic diversity; Genetics of eukaryotes. Biological and molecular evolution; Genome, Bacterial; Genomes; Hospitals; Host-Pathogen Interactions; Human Genetics; Human subjects; Humans; letter; Likelihood Functions; Lipopolysaccharides - genetics; Lung Diseases - microbiology; Microbial mutation; Mutation; Pathogenesis; Pathogens; Phylogeny; Polymorphism, Single Nucleotide; Retrospective Studies; Selection, Genetic; Virulence Factors - genetics; United States; Infection; Human; Pathogenicity; Molecular evolution; Bacteriosis; Bacteria; Candidate gene; Identification
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.997

Roy Kishony and colleagues sequenced the genomes of 112 Burkholderia dolosa isolates recovered from 14 individuals with cystic fibrosis as part of a retrospective study from a hospital epidemic monitored over the course of 16 years. They tracked recurrent mutations occurring in the bacterial isolates and found that 17 genes showed evidence of parallel adaptive evolution. Bacterial pathogens evolve during the infection of their human host 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , but separating adaptive and neutral mutations remains challenging 9 , 10 , 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.