(263c) Distinct Microcolony Morphologies Promote Flow-Dependent Bacterial Colonization

Fluid flows are an important environmental factor that can impact bacterial dynamics across length scales. One example of dramatic responses to fluid flow comes from clinical endocarditis infections. In endocarditis, bacterial vegetations colonize the heart valves and often invasive surgery is needed to replace infected valves. From a fluid dynamics perspective, the valves are the narrowest areas of the heart, which would correspond to the highest shear rates. This observation introduces an intriguing paradox: how are bacterial communities able to survive, and ultimately thrive, in these high shear rate environments?

To study the effect of flow on bacterial communities of Staphylococcus aureus and Enterococcus faecalis, two of the most prevalent endocarditis species, we utilized microfluidics, microscopy, and computational simulations. We discovered bacteria-specific mechanisms that lead to preferential surface colonization in higher shear rate environments, additionally enabling bacteria that are outcompeted in low flow to dominate in high flow. Further analysis of the distinct mechanisms of each species elucidated the impact of the distinct microcolony morphologies of the two species. S. aureus dynamics were driven by transport of a signaling molecule tied to quorum sensing. The clustered microcolonies of S. aureus support local accumulation of signaling molecules, called Autoinducing Peptides (AIPs). As the AIPs reach a quorum, this drives transcriptional responses that leads to cellular dispersal. However, high flow conditions disrupt this signaling, transporting AIPs away from the microcolonies and leading to increased surface colonization by the clustered S. aureus. Conversely, E. faecalis colonization dynamics is driven by mechanical responses on the linear microcolony chains it forms. When these chains experience flow, the torque pushes the chains towards the surface: higher flow rates push the cells closer to the surface, leading to more surface attachment and increased colonization. We further analyzed the different mechanisms by creating two different models- a transport-dependent ODE model for S. aureus dynamics and a mechanics-dependent agent-based model for E. faecalis dynamics. Our discoveries not only elucidate the effect of fluid flow on bacterial dynamics, but also introduces the concept of collective morphologies (i.e. chains or clusters) and the advantages these morphologies can provide in complex fluid flow environments.

In my future work, I will create tractable, host-mimicking microfluidic experiments to observe the interplay between factors such as host proteins, pulsatile flow, and shear rates. Utilizing microscopy, transcriptional profiling, and computational simulations, my lab will understand how these different factors, and their interplay, contribute to bacterial behaviors in fluid flow. This work will expand to other species and other infectious conditions or complex environments, drawing on both my experimental and computational expertise. Furthermore, my lab will broadly examine microcolony morphologies and the advantages (or disadvantages) the morphologies provide in flow and other complex environments.