Parallel Bacterial Evolution Within Multiple Patients Identifies Candidate Pathogenicity Genes

Overview

Journal Nat Genet

Specialty Genetics

Date 2011 Nov 15

PMID 22081229

Citations 249

Authors

Tami D Lieberman

Jean-Baptiste Michel

Mythili Aingaran

Gail Potter-Bynoe

Damien Roux

Michael R Davis Jr

David Skurnik

Nicholas Leiby

John J LiPuma

Joanna B Goldberg

Alexander J McAdam

Gregory P Priebe

Roy Kishony

Affiliations

Soon will be listed here.

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.

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