Biosensors for Quorum Signaling Molecules: Managing Crohn’s Disease

Some bacteria control expression of specialized genes by producing and responding to extracellular signaling molecules in proportion to cell density. This allows pathogens to render an effective attack on the host by ensuring that a “critical mass” of bacteria has been reached. This phenomenon is termed asquorum sensingsince the concentration of the quorum sensing signaling molecule (QSM) is a reflection of the population size. An example of signaling molecules in Gram-negative bacteria are the N-acyl homoserine lactone (AHL) family. Gram-positive bacteria mainly release peptides as signaling molecules. The autoinducer AI-2, a furanosyl borate diester, has been found to be a universal signaling molecule in both Gram-positive and Gram-negative bacteria. Production of signaling molecules occurs during a specific growth stage, in response to changes in the environment such as starvation, or under certain physiological conditions. The presence of bacteria has been shown to be critical in the pathogenesis of Inflammatory Bowel Disease, including Crohn’s Disease (CD), as well as other Gastrointestinal Diseases.

We believe that quorum sensing plays an important role in CD. Given the interplay of bacterial flora and the status of luminal inflammation, the measurement of QSMs may be an attractive tool in the assessment of the inflammatory state. To that end, we are employing genetically engineered bacterial whole-cell sensing systems capable of rapid, sensitive and quantitative detection of different types of QSMs, specifically, long and short chain AHLs as well as AI-2. These sensing systems have been employed in the analysis of saliva, stool and bowel secretion samples from CD patients and matched healthy controls. We are detecting varying levels of AHLs and AI-2 in the samples collected by using a diverse sensing platforms. The possibility of employing QSMs as biomarkers of inflammatory activity in CD is under evaluation. The enrolled CD patients are being followed-up in order to assess the correlation of the QSM activity measured in their saliva and stool with the disease activity. In addition our biosensing systems are employed for the identification of quorum sensing inhibitors as a potential new class of antibiotic agents.