ABSTRACT:
My work explores the role of mechanical forces in bacterial pathogenesis at the interface of biophysics and molecular genetics. During the course of an infection, bacteria encounter a variety of mechanical forces such as adhesive forces during contact with the host cells that they infect and shear stresses in fluidic environments. Using a mechano-genetic approach that I have developed, I found that bacteria use mechanical cues (1) to detect the presence of host cells and (2) to guide the expansion of large bacterial populations within host organisms. In particular, my work shows that the major pathogen Pseudomonas aeruginosa detects the presence of host cell surfaces, akin to a bacterial sense of touch. This mechanical cue activates virulence and consequently P. aeruginosa, unlike other pathogens, does not rely on a chemical signal specific to any one host. This novel paradigm provides a long-sought explanation for understanding how P. aeruginosa can infect a broad range of hosts including humans, animals and plants. My findings highlight mechano-sensation as an important signaling class for pathogenesis and suggest alternative strategies for combatting bacterial infections. The ubiquity and diversity of mechanical forces in all aspects of a bacterium’s life have far-reaching consequences within and beyond pathogenesis and thus constitutes an important novel avenue of research. Moving forward, my laboratory will employ mechano-genetic techniques to understand how diverse bacteria sense, interpret and translate mechanical signals.
Department of Molecular Biology, Princeton University