A surface-induced asymmetric program promotes tissue colonization by Pseudomonas aeruginosa

The opportunistic human pathogen Pseudomonas aeruginosa effectively colonizes host epithelia using pili as primary adhesins. Here we uncover a surface-specific asymmetric virulence program that greatly enhances P. aeruginosa host colonization. We show that when P. aeruginosa encounters surfaces, the concentration of the second messenger c-di-GMP increases within a few seconds. This leads to surface adherence and virulence induction by stimulating pili assembly through the activation of the c-di-GMP receptor FimW. Surface attached bacteria divide asymmetrically generating a piliated, surface committed progeny and a flagellated, motile offspring that leaves the surface to colonize distant sites. Cell differentiation is driven by a phosphodiesterase that asymmetrically positions to the flagellated pole thereby maintaining c-di-GMP levels low in the motile offspring. Infection experiments demonstrate that cellular asymmetry strongly boosts infection spread and tissue damage. Thus, P. aeruginosa promotes surface colonization and infection transmission through a cooperative virulence program that we termed Touch-Seed-and-Go.