Date of Award

Fall 2012

Project Type

Thesis

Program or Major

Microbiology

Degree Name

Master of Science

First Advisor

Vaughn Cooper

Abstract

How diversity evolves and persists in biofilms is essential for understanding much of microbial life, including the uncertain dynamics of chronic infections. We developed a novel biofilm model enabling long-term selection for daily adherence to and dispersal from a plastic bead in a test tube. Focusing on a pathogen of the cystic fibrosis (CF) lung, Burkholderia cenocepacia, we sequenced clones and metagenomes to unravel the mutations and evolutionary forces responsible for adaptation and diversification of a single biofilm community during 1050 generations of selection. The mutational patterns revealed recurrent evolution of biofilm specialists from generalist types and multiple adaptive alleles at relatively few loci. Fitness assays also demonstrated strong interference competition among contending mutants. Metagenomes from five other independently evolved biofilm lineages revealed extraordinary mutational parallelism that outlined common routes of adaptation; these mutations in turn were surprisingly well represented among mutations that evolved in CF isolates of both Burkholderia and Pseudomonas. These convergent pathways included altered metabolism of cyclic di-GMP, polysaccharide production, TCA cycle enzymes, global transcription, and iron scavenging. Evolution in chronic infections may therefore be driven by selection for both biofilm formation and dispersal, which lends hope that experimental evolution may illuminate the ecology and selective dynamics of chronic infections and improve treatment strategies.

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