Rhamnolipids Are Virulence Factors That Promote Early Infiltration of Primary Human Airway Epithelia by Pseudomonas aeruginosa

The opportunistic bacterium Pseudomonas aeruginosa causes chronicrespiratory infections in cystic fibrosis and immunocompromisedindividuals. Bacterial adherence to the basolateral domain of the hostcells and internalization are thought to participate in P.aeruginosa pathogenicity. However, the mechanism by which thepathogen initially modulates the paracellular permeability of polarizedrespiratory epithelia remains to be understood. To investigate thismechanism, we have searched for virulence factors secreted by P.aeruginosa that affect the structure of human airway epithelium inthe early stages of infection. We have found that only bacterialstrains secreting rhamnolipids were efficient in modulating the barrierfunction of an in vitro-reconstituted human respiratory epithelium,irrespective of their release of elastase and lipopolysaccharide. Incontrast to previous reports, we document that P. aeruginosawas not internalized by epithelial cells. We further report thatpurified rhamnolipids, applied on the surfaces of the epithelia, weresufficient to functionally disrupt the epithelia and to promote theparacellular invasion of rhamnolipid-deficient P. aeruginosa.The mechanism involves the incorporation of rhamnolipids within thehost cell membrane, leading to tight-junction alterations. The studyprovides direct evidence for a hitherto unknown mechanism whereby thejunction-dependent barrier of the respiratory epithelium is selectivelyaltered byrhamnolipids.