The regulation of natural competence for DNA uptake and gene transfer in Salmonella and related bacteria

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OBJECTIVE: The proposed program will improve our understanding of how, when, and why many bacteria consume extracellular DNA using a process called "natural competence". Although widespread, the contributions of natural competence to bacterial ecology and genome evolution remain poorly understood and poorly quantified. We seek to fill these large gaps in our understanding of DNA uptake, gene transfer, and DNA metabolism using well-studied species that have so far been overlooked in studies of natural competence. BACKGROUND: Natural competence is a specialized and dedicated process involving active binding and translocation of DNA across the bacterial cell envelope. Once inside, DNA can recombine with the host genome, resulting in horizontal gene transfer through "natural transformation". Horizontal gene transfer has broad and strong influences on genome evolution and niche expansion in bacteria. Escherichia coli, Salmonella, and their relatives are a group of adaptable bacteria that regularly transition between diverse environments. Members of this family evolve quickly through the acquisition of pathogenicity and antimicrobial resistance genes by horizontal gene transfer, but there is no knowledge of how often or when gene transfer through natural competence and transformation. DNA uptake provides valuable nutrients, and natural competence has been shown to support E. coli growth in nutrient limited environments, suggesting that competence has multiple ecological roles and consequences, from gene transfer to nutrient acquisition. Our goal is to identify and characterize the molecular networks that link competence gene regulatory mechanisms to environmental and physiological signals in E. coli and Salmonella, and related bacteria. As we develop the abilities to naturally and artificially stimulate competence, we will quantify how DNA uptake contributes to gene transfer and nutrient acquisition in different bacterial environments. SCIENTIFIC APPROACH: This NSERC Discovery proposal addresses three integrated goals for studying Enterobacteriaceae. First, we will determine how natural competence is regulated in response to environmental and physiological signals. Second, we will quantify how natural competence contributes to horizontal gene transfer and genome evolution. And third, we will quantify how natural competence contributes to nutrient acquisition by bacteria in pure and mixed-species communities. SIGNIFICANCE: Our Discovery program is poised to elucidate an ancient yet cryptic process in Salmonella, E. coli, and related bacteria. Natural competence is conserved over long evolutionary times and in diverse niches, indicating fundamental yet uncharacterized contributions to bacterial survival. The proposed Discovery program will build from our recent achievements to advance the study of natural competence and gene transfer.