EFRI-MIKS: Deciphering and Controlling the Signaling Processes in Bacterial Multicellular Systems and Bacteria-Host Interactions

Syracuse University, Syracuse NY

Investigators

Abstract

1137186 Ren Intellectual Merit: Bacteria are well known to obtain intrinsic tolerance to antibiotics and disinfectants by forming surfaceattached sessile colonies embedded in an extracellular matrix, known as biofilms, and by forming metabolically inactive cells, known as persister cells. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms, presenting a great challenge to microbial control. Despite the well recognized significance, research on biofilms and persister cells is still in its infancy. Distribution of persisters in biofilms and the effects of environmental/host factors and cell-cell signaling on such distribution and biofilm-associated stress tolerance are unknown, mostly due to the heterogeneity in biofilm structure, spatial and temporal variation in gene expression, and redundancy in persister and biofilm genes. The objective of this EFRI project is therefore to understand and manipulate the multicellular and inter-kingdom signaling processes in such complex systems by addressing these key challenges using well integrated multidisciplinary approaches. Based on recent successes in surface engineering, patterned biofilm formation, systems biology and molecular simulation, this research team will conduct the first-of-its-kind research to: (1) systematically characterize persister formation during biofilm development, (2) identify the roles of key genes and signaling processes in persister formation, (3) develop an unprecedented computational capability to accurately predict signaling factor translocation through the extracellular matrix of the biofilms, and (4) synthesize and characterize functional nanoparticles for controlled release of signaling modulators to eliminate persister cells. A number of important questions will be answered for the first time. These discoveries will have a transformative impact in designing more effective knowledge-based strategies for the manipulation and control of bacterial multicellular behaviors and bacteria-host interactions. Broader Impacts: In addition to fundamental understanding of biofilm development and persister formation, the findings from this study will also improve the general knowledge of bacterial physiology with the potential to shift the paradigm of microbial control. Furthermore, the results of this research as pertains to deleterious biofilms of pathogenic and corrosive bacteria can be extended to the development of better biofilm systems of environmentally friendly bacteria, which have broad applications in bioremediation of toxic chemicals and economical production of renewable biofuels. Due to the broad spectrum of problems and opportunities associated with persister cells and biofilms, the proposed work will have significant impacts on basic science, economy, biosecurity and health care. Beyond any technical achievements, this project will also play an important role in transforming college engineering education. Unlike traditional projects that focus on relatively narrow topics, this project targets multicellular and inter-kingdom signaling, a highly interdisciplinary area. The advanced topics associated with this research will provide invaluable materials to teach modern biotechnology, molecular simulation, synthetic biology and bioinformatics, providing the students with crucial knowledge and skills to address the scientific, engineering and societal challenges. This research will also create exciting outreach opportunities and bring talented young people, especially underrepresented groups, into science and engineering careers.