Two-component signal transduction (TCST) pathways are the predominant means bacteria use to sense environmental changes and subsequently adapt to those perceived changes. Additionally, in pathogenic bacteria, these signal transduction pathways are often critical in controlling the expression of bacterial genes mediating disease pathogenesis. The maintenance of insulation of individual TCST pathways from interference by signals affecting other TCST pathways is often considered paramount in allowing bacteria to respond appropriately to any environmental cue. Data from our lab, and the labs of others, now suggest that distinct TCST pathways of the gastric pathogenic bacterium Helicobacter pylori, may simultaneously affect the expression of an overlapping set of genes, thus integrating distinct signals in control of specific gene expression. Metabolic pathways regulated to such precision that multiple regulatory mechanisms are required for appropriate expression may reflect previously unrecognized or underappreciated critical points in the physiology of this important human pathogen. The main goals of our project are to 1) characterize the level of cross regulation by various H. pylori TCST pathways using the acetone decarboxylase enzyme encoding operon, acxABC, as a primary target and 2) use molecular genetic techniques to characterize our proposed regulon for the H. pylori TCST pathway, CrdRS and thus test potential environmental signals detected by this signal transduction pathway. We propose to characterize gene expression levels of various CrdRS regulated H. pylori genes in the presence and absence of TCST pathways. This will be accomplished by various means including transcriptional reporter assays, quantitative real time PCR as well as protein-DNA interaction studies.
Pathogenic bacteria use sensory pathways to detect changes in their environment and respond appropriately to those changes. The peptic ulcer disease and gastric cancer causing bacterium, Helicobacter pylori possesses only three such pathways and studies of their role in integrating host environmental conditions and the bacterial metabolism are crucial to our understanding of how this pathogen persists in association with the host, often for the lifetime of the host!
