title: Catechol siderophores repress the pyochelin pathway and activate the enterobactin pathway in Pseudomonas aeruginosa: an opportunity for siderophore-antibiotic conjugates development.
abstract: Previous studies have suggested that antibiotic vectorization by siderophores (iron chelators produced by bacteria) considerably increases the efficacy of such drugs. The siderophore serves as a vector: when the pathogen tries to take up iron via the siderophore, it also takes up the antibiotic. Catecholates are among the most common iron-chelating compounds used in synthetic siderophore-antibiotic conjugates. Using reverse transcription polymerase chain reaction and proteomic approaches, we showed that the presence of catecholate compounds in the medium of Pseudomonas aeruginosa led to strong activation of the transcription and expression of the outer membrane transporter PfeA, the ferri-enterobactin importer. Iron-55 uptake assays on bacteria with and without PfeA expression confirmed that catechol compounds imported iron into P. aeruginosa cells via PfeA. Uptake rates were between 0.3 × 10(3) and 2 × 10(3) Fe atoms/bacterium/min according to the used catechol siderophore in iron-restricted medium, and remained as high as 0.8 × 10(3) Fe atoms/bacterium/min for enterobactin, even in iron-rich medium. Reverse transcription polymerase chain reaction and proteomic approaches showed that in parallel to this switching on of PfeA expression, a repression of the expression of pyochelin (PCH) pathway genes (PCH being one of the two siderophores produced by P. aeruginosa for iron acquisition) was observed.
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gasser
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Baco
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cunrath
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Pamela Saint
authors.initials: PS
authors.lastname: August
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Perraud
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zill
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Schleberger
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Paulen
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bumann
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Gaëtan L A
authors.initials: GL
authors.lastname: Mislin
authors.affiliation: Université de Strasbourg, ESBS, F-67413, Illkirch, France.|UMR 7242, CNRS, F-67413, Illkirch, France.
authors.forename: Isabelle J
authors.initials: IJ
authors.lastname: Schalk
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002396:Catechols / Q000378:metabolism*; D004758:Enterobactin / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D017262:Siderophores / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002396:Catechols; D026901:Membrane Transport Proteins; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; D004758:Enterobactin; C025316:pyochelin; D007501:Iron