Dirhamnolipids secreted from Pseudomonas aeruginosa modify anjpegungal susceptibility of Aspergillus fumigatus by inhibiting β1,3 glucan synthase activity.
Pseudomonas aeruginosa and Aspergillus fumigatus are the two microorganisms responsible for most of the chronic infections in cystic fibrosis patients. P. aeruginosa is known to produce quorum-sensing controlled rhamnolipids during chronic infections. Here we show that the dirhamnolipids secreted from P. aeruginosa (i) induce A. fumigatus to produce an extracellular matrix, rich in galactosaminogalactan, 1,8-dihydroxynaphthalene (DHN)- and pyo-melanin, surrounding their hyphae, which facilitates P. aeruginosa binding and (ii) inhibit A. fumigatus growth by blocking β1,3 glucan synthase (GS) activity, thus altering the cell wall architecture. A. fumigatus in 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 β1,3 GS; however, the site of action of diRhls on GS is different from that of echinocandins, and showed synergistic anjpegungal effect with azoles.
Unité des Aspergillus, Institut Pasteur, Paris, France.
Benoit
B
Briard
Unité des Aspergillus, Institut Pasteur, Paris, France.
Vero
V
Rasoldier
Ultrapole, Institut Pasteur, Paris, France.
Perrine
P
Bomme
Fundación MEDINA, Granada, Spain.
Noureddine
N
ElAouad
Unité de Chimie des Biomolécules and CNRS UMR3526, Institut Pasteur, Paris, France.
Catherine
C
Guerreiro
Unité de Chimie des Biomolécules and CNRS UMR3526, Institut Pasteur, Paris, France.
Pierre
P
Chassagne
Unité des Aspergillus, Institut Pasteur, Paris, France.
Laetitia
L
Muszkieta
Unité des Aspergillus, Institut Pasteur, Paris, France.
Jean-Paul
JP
Latgé
Unité de Chimie des Biomolécules and CNRS UMR3526, Institut Pasteur, Paris, France.
Laurence
L
Mulard
Unité des Aspergillus, Institut Pasteur, Paris, France.
Anne
A
Beauvais
D001232:Aspergillus fumigatus / Q000166:cytology / Q000378:metabolism*; D002473:Cell Wall; D002686:Chitin / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D025301:Hyphae / Q000378:metabolism; D011134:Polysaccharides; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000378:metabolism*; D053038:Quorum Sensing / Q000187:drug effects
D006017:Glycolipids; D011134:Polysaccharides; C062157:galactosaminogalactan; C051310:rhamnolipid hemolysin, Pseudomonas aeruginosa; D002686:Chitin; D005964:Glucosyltransferases; C040232:glucan synthase