Plasmid manipulation of bacterial gene regulatory networks

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Genome sequencing has revealed that bacteria frequently exchange genes between species, speeding-up evolution by allowing it to proceed by big leaps rather than just the gradual accumulation of small changes. Genes often pass from one bacterial cell to another on circular pieces of DNA called plasmids. Acquiring a plasmid is typically costly to a bacterial cell. However, little is currently known about the causes of these fitness costs. One possible cause of fitness costs is that plasmids often carry genes that interfere with the switching on / off of bacterial genes causing these genes to be expressed at the wrong times. In the proposal, we investigate a common plant-associated bacterium, Pseudomonas fluorescens, where gaining a plasmid switches on around 20% of bacterial genes. Our preliminary data links this gene disruption to a widespread global regulatory pathway, Gac/Rsm, which controls the switch between chronic, biofilm-forming lifestyles and acute virulent states in many different bacterial species. This raises the intriguing possibility that plasmid-acquisition may reprogram the Gac/Rsm pathway, impacting key virulence- and competition-related behaviours in diverse bacterial species, including important human and plant pathogens. In this project, we will first unravel the molecular mechanism by which plasmids disrupt bacterial gene expression. Informed by the results of these experiments, we will examine the fitness costs and potential benefits of plasmid acquisition in complex plant-associated environments, and test whether the plasmid benefits from disrupting the Gac/Rsm pathway by boosting its rate of spread in bacterial populations growing on plants. These experiments will shed new light on a fundamental process in bacterial evolution, with relevance for understanding the sharing of genes encoding important functional traits (including antibiotic resistance) in natural communities.