The Roles of Iron, Fur and PerR in Regulating Gene Expression in Campylobacter jejuni

Abstract

Campylobacter jejuni is one of the most frequent causes of gastroenteritis in both the developing and the developed world. Understanding C. jejuni biology is paramount to reducing the amount of Campylobacter jejuni in the food chain, however our understanding of the regulatory networks that enable Campylobacter jejuni to successfully colonize various hosts remains incomplete. Campylobacter jejuni has an absolute requirement for iron in order to grow as iron catalyzes a wide range of essential biochemical reactions. In contrast to many Gram negative bacteria, the genome of Campylobacter jejuni contains two iron activated Fur-family transcriptional regulators, Fur and PerR, which are primarily responsible for regulating iron homeostasis and oxidative stress respectively. We have used an integrated approach that combines genome wide technologies (ChIP-chip, RNA-seq) and structural studies to define the role of iron, Fur and PerR in Campylobacter jejuni. These studies have demonstrated that apo-Fur directly regulates gene transcription in Campylobacter jejuni, identified novel ncRNAs that are Fur and/or iron responsive, and revealed that the Fur and PerR regulons are more extensive than previously characterized. These results provide further insight into the surprisingly complex regulatory networks that allow Campylobacter jejuni to be a successful gut pathogen.