RpoS Regulon Modulation by Environmental Selection

Abstract

<p>Regulatory interactions evolve to incorporate new genomic material and contribute to bacterial diversity. These regulatory interactions are flexible and likely provide bacteria with a means of rapid environmental adaptation. In this thesis, the RpoS regulon is used as a model system to investigate the hypothesis that regulon composition and expression are modified according to environmental pressures. Several novel findings are presented, namely the distribution of RpoS homologs in bacteria, the flexibility of the RpoS regulon, and the effect of diverse environmental pressures on RpoS regulon expression. Based on phylogenetic and reciprocal best hits analyses, RpoS was determined to be conserved in gamma-, beta-, and delta-proteobacteria, likely because it confers a selective advantage in many bacterial niches. Regulon composition, however, was highly flexible. Even between species of the same class, <em>Escherichia coli</em> and <em>Pseudomonas aeruginosa</em>, only 12 of 50 orthologs were regulated in common by RpoS. RpoS regulon flexibility may thus be the result of adaptation to different bacterial habitats. Indeed, mutations in <em>rpoS</em> and differential regulon expression could be identified among environmental <em>E. coli</em> isolates collected from diverse sources. Among environmental <em>E. coli</em> isolates, RpoS mutant frequency was found to be 0.3%, and activity of KatE, a prototypical RpoS regulon member, was undetectable in some isolates despite the presence of functional RpoS. Modulated RpoS regulon expression among environmental <em>E. coli</em> isolates is consistent with environment as a key factor shaping regulatory interactions. Regulon flexibility was similarly apparent in oxidative stress regulons, OxyR and SoxRS, of <em>E. coli</em>. SoxRS regulon function is weakly conserved, possibly due to low selective pressure for a superoxide stress response regulon in some bacterial species. Environment, therefore, is a crucial element that defines the dynamics of regulatory networks.</p>