title: Cell aggregation promotes pyoverdine-dependent iron uptake and virulence in Pseudomonas aeruginosa.
abstract: In Pseudomonas aeruginosa the Gac signaling system and the second messenger cyclic diguanylate (c-di-GMP) participate in the control of the switch between planktonic and biofilm lifestyles, by regulating the production of the two exopolysaccharides Pel and Psl. The Gac and c-di-GMP regulatory networks also coordinately promote the production of the pyoverdine siderophore, and the extracellular polysaccharides Pel and Psl have recently been found to mediate c-di-GMP-dependent regulation of pyoverdine genes. Here we demonstrate that Pel and Psl are also essential for Gac-mediated activation of pyoverdine production. A pel psl double mutant produces very low levels of pyoverdine and shows a marked reduction in the expression of the pyoverdine-dependent virulence factors exotoxin A and PrpL protease. While the exopolysaccharide-proficient parent strain forms multicellular planktonic aggregates in liquid cultures, the Pel and Psl-deficient mutant mainly grows as dispersed cells. Notably, artificially induced cell aggregation is able to restore pyoverdine-dependent gene expression in the pel psl mutant, in a way that appears to be independent of iron diffusion or siderophore signaling, as well as of recently described contact-dependent mechanosensitive systems. This study demonstrates that cell aggregation represents an important cue triggering the expression of pyoverdine-related genes in P. aeruginosa, suggesting a novel link between virulence gene expression, cell-cell interaction and the multicellular community lifestyle.
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome Rome, Italy ; Department of Sciences, Universita degli Studi Roma Tre Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Visaggio
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Pasqua
authors.affiliation: Department of Sciences, Universita degli Studi Roma Tre Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Bonchi
authors.affiliation: Research Core Unit Metabolomics, Institute of Pharmacology, Hannover Medical School Hannover, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Department of Sciences, Universita degli Studi Roma Tre Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Visca
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome Rome, Italy ; Pasteur Institute - Cenci Bolognetti Foundation, Sapienza University of Rome Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Imperi
keywords: Pseudomonas aeruginosa; cell aggregates; extracellular polysaccharide; gene regulation; iron uptake; mechanosensor; siderophore; virulence