A Surface-Induced Asymmetric Program Promotes Tissue Colonization by Pseudomonas aeruginosa

Abstract

The opportunistic human pathogen Pseudomonas aeruginosa effectively colonizes host epithelia using pili as primary adhesins. Here we uncover a surfacespecific 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.

Cell‐Wall‐Targeting Antibiotics Cause Lag‐Phase Bacteria to Form Surface‐Mediated Filaments Promoting the Formation of Biofilms and Aggregates

“…Our findings, of surface‐driven growth of filaments, suggest that the fimbriae/pili‐initiated attachment is required for lag‐phase bacteria to divide continuously without separation—a correlation yet to be elucidated. A particularly interesting finding is that surface attachment can cause “asymmetric cell divisions”, through which a bacterium adhering to a surface to can generate two different daughter phenotypes . Thus, the progeny within each filament grown on a surface is an interesting topic for exploration.…”

The Xanthomonas oryzae pv. oryzae type IV pilus alignment subcomplex protein PilN contributes to regulation of bacterial surface‐associated behaviours and T3SS system

“…citri, it has been indicated that the PilZ-FimX EAL -c-di-GMP complex is responsible for regulation of T4P biogenesis (Guzzo et al, 2013). Recent findings showed that the P. aeruginosa fimW encoding a PilZ protein, adjacent to fimX in the chromosome, is a c-di-GMP high-affinity binding protein and regulates T4P dynamics, as well as being necessary for T4P-based attachment (Laventie et al, 2019). Cryoelectron tomography combined with protein-protein interaction assays revealed that the N terminus of PilN binds to PilM in the cytoplasm, then PilM binds to PilT and PilB, two ATPases that power assembly and disassembly of T4P, respectively (Kolappan et al, 2016).…”

“…Recent studies indicated that some pathogens are able to induce virulence genes expression on surface contact, and that T4P play an important role in this process (Laventie et al, 2019). One of the major virulence factors of Xoo is the T3SS (Buttner and Bonas, 2010).…”

“…Recent studies in P . aeruginosa indicated that this pathogen rapidly activates a c‐di‐GMP‐dependent surface programme to promote adherent pili and virulence (Laventie et al , ). In addition, PilY1 is able to activate downstream c‐di‐GMP production through the alignment complex PilM‐PilN‐PilO‐PilP and the diguanylate cyclase SadC, thereby inhibiting swarming motility (Kuchma et al , ).…”

“…Moreover, other proteins including a pre-pilin peptidase PilD, a putative ATPase PilU, the two-component system PilS/PilR, the minor pilins FimT, PilV, PilW, PilX, and PilE, and the envelope protein PilY1 (adhesin) are indicated to be connected with the function, structure, and regulation of T4P (Kuchma et al, 2012;Kilmury and Burrows, 2018). Recent studies in P. aeruginosa indicated that this pathogen rapidly activates a c-di-GMP-dependent surface programme to promote adherent pili and virulence (Laventie et al, 2019). In addition, PilY1 is able to activate downstream c-di-GMP production through the alignment complex PilM-PilN-PilO-PilP and the diguanylate cyclase SadC, thereby inhibiting swarming motility (Kuchma et al, 2012).…”