Elasticity promotes directional transport of Pseudomonas aeruginosa in native human airway mucus and complex fluids

Pseudomonas aeruginosa is an opportunistic pathogen normally cleared by mucus but becomes infectious in mucus-obstructive lung diseases, where it forms colonies and biofilms. Although motility is essential for biofilm formation, its transport in native mucus remains poorly understood. Existing studies on mucus-bacteria interactions and P. aeruginosa transport within mucus largely rely on reconstituted mucus or purified mucins, which have properties dramatically different from native mucus. Here, we investigate the motion of P. aeruginosa strain PA14 in normal and diseased native human airway mucus. Using well-differentiated human bronchial epithelial cultures, we harvest native mucus replicating healthy and pathological conditions and develop a droplet-in-oil system to quantify single bacterium motion. Surprisingly, highly viscoelastic normal mucus promotes directional motility at speeds comparable to those in low viscosity buffer, whereas concentrated pathological mucus with dominant elasticity traps bacteria and reduces motility over tenfold. Engineering mucus simulants with decoupled viscosity and elasticity reveals that elasticity induces a qualitative change of bacterial motility from circular to directional motion. Our discovery not only provides insights into the biophysical mechanisms of bacterial infection in the lung but also reveals the previously unrecognized importance of elasticity in directional bacterial transport within complex fluids.