Grant: Operating Grant

Diarrhea caused by bacteria is a major cause of childhood mortality world-wide. Bacteria that cause diarrhea, such as Escherichia coli and Vibrio cholerae must survive many different potentially harmful environments during infection in order to cause disease. For example, the stomach is extremely acidic and humans produce antibacterial compounds during infection. My research group studies the mechanisms used to sense and adapt to noxious stressors that can damage the bacterial cell. We have identified one stress response, the Cpx envelope stress response, that plays a conserved role in multiple pathogens in adapting to diverse stresses that damage proteins in the outermost compartment of the cell, the envelope. When the Cpx response is turned on, two key bacterial attributes that determine disease outcome are affected, virulence factor production and antibiotic resistance. We have identified genes that we hypothesize are involved in turning off the production of virulence factors that also impact antibiotic resistance. We propose to test the roles of these genes in E.coli and V. cholerae pathogenesis and antibiotic resistance, and study the events that regulate their expression. The ultimate goal of our work is to uncover new targets for the development of future preventative or therapeutic strategies to treat diarrhea that is caused by bacteria.