Bacterial Transport Under Confinement: New Paradigms in Microbial Competition and Host Response

Extreme physical confinement fundamentally reshapes microbiota structure and competition by modulating bacterial transport, for instance, in the intestinal crypts, which are preferentially targeted by infectious bacteria. Once a bacterium penetrates a narrow pore with a cross-section matching its width, the cell can enjoy long-term protection from fluid entrainment and large predators, such as immune cells. How steric exclusion and hydrodynamic forces influence single-cell access to such narrow spaces remains unknown. I will discuss our recent discoveries, revealing how motile bacteria use self-propulsion to transform rigid, narrow pores into virtual funnels, thereby facilitating penetration by several orders of magnitude. Virtual funneling is preceded by the cell scanning the surface for an opening, a process analogous to an RNA polymerase decreasing the dimensionality of its search for a promoter via a random walk along the DNA. Strikingly, we have observed that extreme confinement increases the swimming speed of specific types of bacteria by 100-150%, a discovery that is at odds with expectations of decreased motility given the 30-50-fold increase in viscous drag within the pore. We have leveraged such species-specific motility characteristics to develop an Artificial Intelligence-Imaging platform for 2-minute bacterial phenotyping, opening new avenues for continuous monitoring of antibiotic resistance and infections. I will discuss how these discoveries underpin and advance emerging frontiers in microbial adaptation, enzymatic catalysis, biofilm formation, and immune cell-bacterial interactions.