This award by the Biomaterials Program of the Division of Materials Research to Iowa State University is to study novel polymeric nanoparticles to suppress bacterial quorum sensing (QS). Through QS, bacteria recognize each others' presence by detecting auto-inducers secreted into the immediate environment. Once a threshold concentration is reached for the auto-inducers, QS-regulated genes are turned on to trigger biofilm formation and enhanced virulence for pathogenic bacteria. In biofilms, bacteria can be 1000-times more resistant to antibiotics and other environmental pressure. Eighty percent of all bacterial infections are related to biofilm formation and practically all medical devices are subject to biofilm infection. Overcoming bacterial resistance and biofilm formation is an urgent and difficult challenge to scientists and engineers worldwide. The proposed research aims to develop nanoparticle catalysts to mimic naturally occurring auto-inducer degrading enzymes to selectively destroy the main auto-inducer of gram negative bacteria. The research has the potential to impact numerous areas that are affected by bacterial biofilm formation including health care, engineering, and agriculture. This cross disciplinary research will expose student researchers to a wide range of skills and prepare them to solve large problems faced by humanity through cutting edge materials research.
Despite their unicellular nature, bacteria can communicate with each other and recognize others' presence. The process, termed quorum sensing (QS), happens as signal molecules (i.e., auto-inducers) are secreted and accumulate within a bacterial community. A threshold concentration of the auto-inducer triggers biofilm formation and enhanced virulence for pathogenic bacteria. The emergence of multidrug resistant bacteria and shortage of new antibiotics in drug development prompted many researchers to search intensely for potential solutions, targeting bacteria in the biofilm state in particular. The proposed research develops polymeric nanoparticle catalysts to selectively bind and destroy the main auto-inducer of gram negative bacteria. A number of strategies will be pursued to create catalytic pockets in water soluble nanoparticles carrying the necessary catalytic functionalities for the intended chemical decomposition. Kinetic studies in the degradation of the auto-inducers will be combined with biological assays to identify the most potent biofilm inhibitors. With the proposed research, student researchers will be trained in a wide range of skills including organic synthesis, biology, antimicrobial research, enzyme catalysis, physical organic chemistry, supramolecular chemistry, and polymer chemistry. Moreover, the students will see a strong connection between their work and large problems faced by humans and appreciate the value of cutting edge scientific research. The multidisciplinary work thus can provide excellent training to the student researchers that come from either a chemistry or veterinary medicine background.
