BACTERIAL COLONIZATION ON SURFACES: FROM INFECTION TO PREVENTION

Abstract

Bacteria colonize surfaces using a remarkable array of mechanisms including surface attachment, motility, biofilm formation, and quorum sensing. Surface-attached bacteria multiply, secrete a surrounding matrix, and adhere to one another to form organized communities called biofilms. In this thesis, we present colonization mechanisms that bacteria enact, and show how physical and chemical influences on them make surprising discoveries and potential strategies to manipulate bacterial colonization.

The first chapter of this thesis investigates how Staphylococcus aureus rapidly forms flow-induced, filamentous biofilm streamers under flow in non-uniform geometries, and furthermore, if surfaces are coated with blood plasma, S. aureus streamers appear more rapidly than in uncoated channels.

Surface-attached bacteria sometimes move over surfaces as part of the process of colonization. Surprisingly, Pseudomonas aeruginosa can move on surfaces in the opposite direction of fluid flow. Here, we explore how P. aeruginosa communities use motility to rapidly disperse throughout vasculature-like flow networks. Motility provides P. aeruginosa a selective growth advantage, enabling it to self-segregate in locations distinct from pathogens that outcompete P. aeruginosa in well-mixed non-flow environments. We define the mechanism underlying upstream surface movement and we develop chemical modifications of the surface to inhibit P. aeruginosa from dispersal.

Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors, such as surface motility, biofilm formation, and virulence factor production. Quorum sensing relies on the production, release, and group-wide detection of extracellular signaling molecules called autoinducers. Fluid flow and non-uniform surfaces are ubiquitous in environments occupied by bacteria, most notably in hosts. We show that bacterial colonization under flow in complex topography can lead to heterogeneous quorum-sensing phenotypes, which promotes diversity in the genetic programs that bacteria enact. Consequently, genetically identical bacteria exhibit remarkably different pathogenic behaviors in particular regions and at particular times under flow.

Finally, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. Our studies highlight how this approach can be used to control colonization behaviors of bacteria on surfaces.