Colonization, Competition, and Dispersal of Pathogens in Fluid Flow Networks

Abstract

SUMMARY The colonization of bacteria in complex fluid flow networks, such as those found in host vasculature, remains poorly understood. Recently, it was reported that many bacteria, including Bacillus subtilis [1], Escherichia coli [2], and Pseudomonas aeruginosa [3, 4], can move in the opposite direction of fluid flow. Upstream movement results from the interplay between fluid shear stress and bacterial motility structures and such rheotactic-like behavior is predicted to occur for a wide range of conditions [1]. Given the potential ubiquity of upstream movement, its impact on population-level behaviors within hosts could be significant. Here, we find that P. aeruginosa communities use a diverse set of motility strategies, including a novel surface motility mechanism characterized by counter-advection and transverse diffusion, to rapidly disperse throughout vasculature-like flow networks. These motility modalities give P. aeruginosa a selective growth advantage, enabling it to self-segregate from other human pathogens such as Proteus mirabilis and Staphylococcus aureus that outcompete P. aeruginosa in well-mixed non-flow environments. We develop a quantitative model of bacterial colonization in flow networks, confirm our model in vivo in plant vasculature, and validate a key prediction that colonization and dispersal can be inhibited by modifying surface chemistry. Our results show that the interaction between flow mechanics and motility structures shapes the formation of mixed-species communities and suggest a general mechanism by which bacteria could colonize hosts. Furthermore, our results suggest novel strategies for tuning the composition of multi-species bacterial communities in hosts, preventing inappropriate colonization in medical devices, and combatting bacterial infections.

Local and global consequences of flow on bacterial quorum sensing

“…Our findings suggest that, compared with the no-flow scenario in which QS-mediated communication is driven exclusively by diffusion, the transport of autoinducers by flow in confined configurations increases the length scale of bacterial communication so that QS-directed processes are non-uniform along natural flow pathways. This finding might explain why Pseudomonas aeruginosa is motile upstream (a QS-off phenotype), but forms biofilms downstream (a QS-on phenotype) in flowing networks 24 .…”

The Mechanical World of Bacteria

“…Populations of curved cells thus form robust biofilms more rapidly than straight cells, such that curvature may be viewed as adaptive not only at the scale of a single colonizing bacterium but at the scale of clonal populations descended from surface-associated founder cells. Similarly, the upstream motility of single P. aeruginosa cells provides a group-level advantage when competing with planktonic cells and other species during colonization of fluidic networks (Siryaporn et al, 2015). Phenotypes that evolved in response to mechanical forces experienced by single surface-attached cells could thus contribute to pathogenic infection by a large bacterial population.…”

Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulence

“…An ability to use T4P for twitching motility allows P. aeruginosa to move “upstream” against flow in microfluidic devices [23]. In branched microfluidic systems, twitching motility allows P. aeruginosa cells to move perpendicular to the direction of flow and gain access to side branches.…”