title: Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa.
abstract: Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544;
authors.forename: Alexandre
authors.initials: A
authors.lastname: Persat
authors.affiliation: Department of Medicine, University of California, San Francisco, CA 94143; Microbial Pathogenesis and Host Defense Program, University of California, San Francisco, CA 94143;
authors.forename: Yuki F
authors.initials: YF
authors.lastname: Inclan
authors.affiliation: Department of Medicine, University of California, San Francisco, CA 94143; Microbial Pathogenesis and Host Defense Program, University of California, San Francisco, CA 94143; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143;
authors.forename: Joanne N
authors.initials: JN
authors.lastname: Engel
authors.affiliation: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Stone
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544; zgitai@princeton.edu.
authors.forename: Zemer
authors.initials: Z
authors.lastname: Gitai
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology; D055592:Biophysical Phenomena; D000242:Cyclic AMP / Q000378:metabolism; D036781:Fimbriae Proteins / Q000235:genetics / Q000502:physiology; D010861:Fimbriae, Bacterial / Q000145:classification / Q000502:physiology*; D005798:Genes, Bacterial; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009876:Operon; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D020409:Molecular Motor Proteins; D037521:Virulence Factors; D036781:Fimbriae Proteins; D000242:Cyclic AMP
keywords: mechanotransduction; surface sensing; type IV pili; virulence