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

弹性促进铜绿假单胞菌在天然人类呼吸道粘液和复杂液体中的定向运输

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Abstract

Pseudomonas aeruginosa is an opportunistic bacterium that is readily cleared by mucus clearance in healthy individuals but becomes infectious in patients with mucus obstructive lung diseases, which are characterized by the formation of bacterial colonies or biofilms. The motility of P. aeruginosa is critical for biofilm formation, but it remains poorly understood how the bacterium transports within native mucus. 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 report the transport of P. aeruginosa strain PA14, a human clinical isolate responsible for chronic lung infections, in normal and diseased native human airway mucus. We use well-differentiated human bronchial epithelial cells cultured at the air-liquid-interface to secrete and harvest native human airway mucus with concentrations matching health and disease states. Furthermore, we develop a droplet-in-oil system for quantifying the transport of individual bacterium within bulk mucus. Remarkably, highly viscoelastic normal mucus promotes directional bacterial motility at a speed comparable to that in a low-viscosity physiological buffer. By contrast, concentrated, pathological mucus with elasticity dominating viscosity traps bacteria, reducing their motility more than 10-fold. Engineering mucus simulants with decoupled viscosity and elasticity reveals that the elasticity of complex fluids 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.

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