Enterobactin (ENT) is a tris-catechol siderophore used to acquire iron by multiple bacterial species. These ENT-dependent iron uptake systems have often been considered as potential gates in the bacterial envelope through which one can shuttle antibiotics (Trojan horse strategy). In practice, siderophore analogues containing catechol moieties have shown promise as vectors to which antibiotics may be attached. Bis- and tris-catechol vectors (BCVs and TCVs, respectively) were shown using structural biology and molecular modeling to mimic ENT binding to the outer membrane transporter PfeA in Pseudomonas aeruginosa. TCV but not BCV appears to cross the outer membrane via PfeA when linked to an antibiotic (linezolid). TCV is therefore a promising vector for Trojan horse strategies against P. aeruginosa, confirming the ENT-dependent iron uptake system as a gate to transport antibiotics into P. aeruginosa cells.

Hijacking of the Enterobactin Pathway by a Synthetic Catechol Vector Designed for Oxazolidinone Antibiotic Delivery in Pseudomonas aeruginosa

Milenkovic S.;Ceccarelli M.;
2022-01-01

Abstract

Enterobactin (ENT) is a tris-catechol siderophore used to acquire iron by multiple bacterial species. These ENT-dependent iron uptake systems have often been considered as potential gates in the bacterial envelope through which one can shuttle antibiotics (Trojan horse strategy). In practice, siderophore analogues containing catechol moieties have shown promise as vectors to which antibiotics may be attached. Bis- and tris-catechol vectors (BCVs and TCVs, respectively) were shown using structural biology and molecular modeling to mimic ENT binding to the outer membrane transporter PfeA in Pseudomonas aeruginosa. TCV but not BCV appears to cross the outer membrane via PfeA when linked to an antibiotic (linezolid). TCV is therefore a promising vector for Trojan horse strategies against P. aeruginosa, confirming the ENT-dependent iron uptake system as a gate to transport antibiotics into P. aeruginosa cells.
2022
enterobactin
iron uptake
linezolid
Pseudomonas aeruginosa
siderophore
Trojan horse strategy
Anti-Bacterial Agents
Catechols
Iron
Membrane Transport Proteins
Pseudomonas aeruginosa
Siderophores
Enterobactin
Oxazolidinones
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/345775
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