Bacterial stress responses and surface adhesion in shear flow

Project Summary My research group combines traditional molecular biology approaches with microfluidic technology to examine how host-relevant shear flow impacts stress responses and surface adhesion of the human pathogen Pseudomonas aeruginosa. While reductionist experimental systems provide great mechanistic insight, they commonly lack key aspects of natural systems, such as fluid flow. Thus, there is a great opportunity to solve outstanding problems in microbiology by implementing experimental systems that more precisely model natural conditions. Two major recent discoveries from my lab highlight the scientific opportunities of studying bacteria in flow. First, we discovered that flow sensitizes P. aeruginosa to host-relevant doses of hydrogen peroxide (H2O2). Second, we discovered that host- relevant shear forces counter-intuitively enhance P. aeruginosa adhesion by counteracting pilus-driven surface departure. Over the next five-year funding period, we will use our microfluidic platform to build on these discoveries and investigate three key research gaps: how spatial H2O2 gradients impact bacterial communities (Project 1), how temporal dynamics of H2O2 stress responses are regulated in P. aeruginosa (Project 2), and how type IV pilus retraction promotes surface departure of P. aeruginosa in flow (Project 3). These projects will provide mechanistic answers to questions related to the basic biology of P. aeruginosa and will lay a clear foundation for innovative advances in the treatment of bacterial infections.