(489ai) Counterintuitive Effects of Quorum Sensing On Biofilm Antibiotic Tolerance

Biofilms are thought to be involved in more than half of all medical infections and cost the U.S. healthcare system billions of dollars every year. Interrupting bacterial communication is thought to have great potential as an effective biofilm treatment strategy. This cell-cell communication, known as quorum sensing, has been found to play a critical role in the regulation of many gene functions including those associated with virulence factors. This study focuses on the role of quorum sensing in Escherichia coli K-12 biofilm formation and antibiotic tolerance. Four different experimental strains where constructed by removing key genes from the lsrR mediated AI-2 quorum sensing operon and the AI-2 synthesis circuit. The role quorum sensing plays in biofilm antibiotic tolerance was tested with the no shear colony biofilm system. Contrary to conventional wisdom, disrupting some AI-2 quorum sensing circuit genes made the strains 105-107 of times more tolerant to common antibiotics like ampicillin or kanamycin as compared to wild type cells. The antibiotic tolerance effect was studied under different culturing environments and found to vary up to ten million fold with different medium, antibiotics, and with the different quorum sensing gene knock-out strains. Examination of these variables gives a critical insight into the realm of bacterial communication and its role in biofilm antibacterial resistance. This work identifies key parameters for tailoring, rational, environment-specific antimicrobial drug delivery strategies for controlling problematic biofilms.