Genome-wide mapping of cAMP receptor protein binding in enteroaggregative reveals targeting of virulence-associated genes.

Bacterial pathogens employ a diverse array of virulence factors to colonize and subsequently elicit disease in their host. These factors are often subject to extensive regulation at the transcriptional level to ensure that their expression is timely. Although many pathogens use bespoke transcription factors that primarily target virulence genes, global transcription factors also sometimes play a role in controlling these genes. Enteroaggregative (EAEC) is a significant cause of watery and mucoid diarrhoea globally. The organism colonizes the small intestine before producing toxins that elicit disease, using a multitude of virulence factors that are encoded both chromosomally and on virulence plasmids. In this work, we have studied the cAMP receptor protein (CRP), a well-characterized bacterial global transcription factor, focusing on its role in the pathogenicity of the prototype EAEC strain 042. We show that, although most functional CRP binding sites on the chromosome are conserved between K-12 and 042, CRP has been co-opted to couple the expression of some virulence genes to the nutritional state of the cell. We report novel mechanisms for CRP-dependent regulation of genes whose products contribute to the maturation of a bacterial antibiotic, export of a polysaccharide capsule and production of a putative adhesin.