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Design of Surfaces that Prevent Bacterial Communication and Biofilm Growth

The ability of bacteria to communicate with themselves and function as a group is central to the development of infectious disease. Over the past 30 years, it has become clear that bacteria communicate by assessing their local population densities through a phenomenon known as ‘quorum sensing’ (QS). Many of the most notorious human pathogens use this sensing mechanism to organize into structured communities called ‘biofilms’ and activate virulence pathways that are the basis for acute and chronic infections. As a result, quorum sensing presents an important and relevant target for the development of new anti-infective strategies. This approach is also particularly attractive because it provides a potential means to avoid evolved-resistance mechanisms that plague currently used bactericidal agents (e.g., antibiotics).

From a clinical standpoint, bacterial growth and the formation of biofilms on the surfaces of indwelling medical devices and disposable products represent two primary points of entry for bacteria into the body. Approaches aimed at inhibiting or attenuating quorum sensing in bacteria at or near the surfaces of these objects present a fundamentally new approach to preventing human infection that could lead to new strategies for treating human diseases. In collaboration with colleagues at UW, we have developed new materials-based approaches to the localized and surface-mediated release of novel small-molecule inhibitors of quorum sensing (QSIs) that interrupt QS in a model bacrerium (V. fischeri) and prevent the formation of bacterial biofilms or attenuate virulence when incubated in the presence of clinically relevant pathogens (e.g., P. aeruginosa). Our approaches make use of conventional methods for the encapsulation of small-molecule drugs in bulk thin films of degradable polymers (e.g., PLGA, etc.) as well as new materials and other approaches to the fabrication of polymer thin films developed in our laboratory.

These approaches afford different and complementary levels of control over QSI release profiles and are amenable to the fabrication of bioactive coatings on the complex surfaces of biomedical devices and consumer products on which bacterial growth and biofilm formation are endemic. These materials-based approaches to control of bacterial communication thus provide both (i) new tools to study mechanisms of bacterial virulence and biofilm formation, and (ii) methods that can be adopted readily in personal health and biomedical contexts to treat the surfaces of solid and fiber-based materials to inhibit bacterial biofilm formation and other virulence pathways. In addition to materials that attenuate bacterial communication, we are also developing approaches to the design of film-coated surfaces that prevent or disrupt the formation of fungal biofilms.

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