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 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 activation of the c-di-GMP receptor FimW. Surface-attached bacteria divide asymmetrically to generate a piliated, surface-committed progeny (striker) and a flagellated, motile offspring that leaves the surface to colonize distant sites (spreader). 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. [Display omitted] •P. aeruginosa rapidly boosts c-di-GMP upon surface contact to activate adherent pili•Mechanosensation requires a functional flagellar motor to activate c-di-GMP receptors•Surface colonization triggers asymmetric division to generate specialized progeny•Asymmetric divisions promote infection spread and tissue damage Laventie et al. demonstrate that upon host cell contact, Pseudomonas aeruginosa rapidly activates a c-di-GMP-dependent surface program to promote adherence and virulence. Polar localization of c-di-GMP-interacting proteins triggers pili activation. Asymmetric divisions on surfaces produce specialized cell types, a spreader for dissemination and a striker for local tissue damage.