Dirhamnolipids secreted from Pseudomonas aeruginosamodify anjpegungal susceptibility of Aspergillus fumigatusby inhibiting ß1,3 glucan synthase activity

Pseudomonas aeruginosaand Aspergillus fumigatusare the two microorganisms responsible for most of the chronic infections in cystic fibrosis patients. P. aeruginosais known to produce quorum-sensing controlled rhamnolipids during chronic infections. Here we show that the dirhamnolipids secreted from P. aeruginosa(i) induce A. fumigatusto produce an extracellular matrix, rich in galactosaminogalactan, 1,8-dihydroxynaphthalene (DHN)- and pyo-melanin, surrounding their hyphae, which facilitates P. aeruginosabinding and (ii) inhibit A. fumigatusgrowth by blocking ß1,3 glucan synthase (GS) activity, thus altering the cell wall architecture. A. fumigatusin the presence of diRhls resulted in a growth phenotype similar to that upon its treatment with anjpegungal echinocandins, showing multibranched hyphae and thicker cell wall rich in chitin. The diRhl structure containing two rhamnose moieties attached to fatty acyl chain is essential for the interaction with ß1,3 GS; however, the site of action of diRhls on GS is different from that of echinocandins, and showed synergistic anjpegungal effect with azoles.