title: Rhamnolipids are virulence factors that promote early infiltration of primary human airway epithelia by Pseudomonas aeruginosa.
abstract: The opportunistic bacterium Pseudomonas aeruginosa causes chronic respiratory infections in cystic fibrosis and immunocompromised individuals. Bacterial adherence to the basolateral domain of the host cells and internalization are thought to participate in P. aeruginosa pathogenicity. However, the mechanism by which the pathogen initially modulates the paracellular permeability of polarized respiratory epithelia remains to be understood. To investigate this mechanism, we have searched for virulence factors secreted by P. aeruginosa that affect the structure of human airway epithelium in the early stages of infection. We have found that only bacterial strains secreting rhamnolipids were efficient in modulating the barrier function of an in vitro-reconstituted human respiratory epithelium, irrespective of their release of elastase and lipopolysaccharide. In contrast to previous reports, we document that P. aeruginosa was not internalized by epithelial cells. We further report that purified rhamnolipids, applied on the surfaces of the epithelia, were sufficient to functionally disrupt the epithelia and to promote the paracellular invasion of rhamnolipid-deficient P. aeruginosa. The mechanism involves the incorporation of rhamnolipids within the host cell membrane, leading to tight-junction alterations. The study provides direct evidence for a hitherto unknown mechanism whereby the junction-dependent barrier of the respiratory epithelium is selectively altered by rhamnolipids.
authors.affiliation: Department of Cell Physiology and Metabolism, Medical Center, University of Geneva, 1, rue Michel Servet, Geneva 04 CH1211, Switzerland. Laurence.Zulianello@medecine.unige.ch
authors.forename: Laurence
authors.initials: L
authors.lastname: Zulianello
authors.forename: Coralie
authors.initials: C
authors.lastname: Canard
authors.forename: Thilo
authors.initials: T
authors.lastname: Köhler
authors.forename: Dorothée
authors.initials: D
authors.lastname: Caille
authors.forename: Jean-Silvain
authors.initials: JS
authors.lastname: Lacroix
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
mesh_terms: D000328:Adult; D002470:Cell Survival; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D006017:Glycolipids / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D015398:Signal Transduction; D019108:Tight Junctions / Q000648:ultrastructure; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D006017:Glycolipids; D037521:Virulence Factors; C418382:rhamnolipid