Authors: Kenneth A. Cornell
Affiliation:
Title: Microbial Cross-talk: Natural and Unnatural Messages
Abstract:The continued rise of antibiotic resistant pathogens necessitates the development of new drugs that act against microbe specific processes. A new area of investigation examines the role of microbial communication or "quorum sensing" pathways in the regulation of drug resistance phenotypes and the formation of biofilms that are a source of chronic infection. We have identified potential inhibitors that target quorum sensing pathways by looking at natural precursors and analogs of signal molecules as well as peptides that are absent from the known protein databases. In addition, we have begun to examine the role of a key enzyme, 5' methylthioadenosine / S-adenosylhomocysteine nucleosidase (MTN) on quorum sensing dependent processes. To do this, we have been studying MTN gene knockout strains in E. coli to determine the effect of pathway interruption on microbial biofilms, drug resistance, and autoinducer II formation. Our investigations indicate that either genetic or pharmacologic interruption of the pathway leads to significant effects on microbial growth, biofilm formation and autoinducer type II production. The implications of these studies for the development of new antibiotics and vaccines will be presented and discussed.