Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes
Top Cited Papers
Open Access
- 13 November 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 43 (12), 1275-1280
- https://doi.org/10.1038/ng.997
Abstract
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 host1,2,3,4,5,6,7,8, but separating adaptive and neutral mutations remains challenging9,10,11. 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.Keywords
This publication has 40 references indexed in Scilit:
- Phylogenetic and metabolic diversity of bacteria associated with cystic fibrosisThe ISME Journal, 2010
- A comprehensive catalogue of somatic mutations from a human cancer genomeNature, 2009
- Genome evolution and adaptation in a long-term experiment with Escherichia coliNature, 2009
- Global discovery of adaptive mutationsNature Methods, 2009
- A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patientsProceedings of the National Academy of Sciences, 2008
- High-throughput sequencing provides insights into genome variation and evolution in Salmonella TyphiNature Genetics, 2008
- Bacterial pathogenomicsNature, 2007
- Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencingProceedings of the National Academy of Sciences, 2007
- Tests of parallel molecular evolution in a long-term experiment withEscherichia coliProceedings of the National Academy of Sciences, 2006
- Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patientsProceedings of the National Academy of Sciences, 2006