Siderophores as drug delivery agents: application of the "Trojan Horse" strategy

Möllmann, Ute; Heinisch, Lothar; Bauernfeind, Adolf; Kohler, Thilo; Ankel-Fuchs, Dorothe

doi:10.1007/s10534-009-9219-2

Scientific article

English

Siderophores as drug delivery agents: application of the "Trojan Horse" strategy

Contributors

Möllmann, Ute; Heinisch, Lothar; Bauernfeind, Adolf; Kohler, Thilo

; Ankel-Fuchs, Dorothe

Published in

BioMetals, vol. 22, no. 4, p. 615-624

Publication date

2009

Abstract

The outer membrane permeability barrier is an important resistance factor of bacterial pathogens. In combination with drug inactivating enzymes, target alteration and efflux, it can increase resistance dramatically. A strategy to overcome this membrane-mediated resistance is the misuse of bacterial transport systems. Most promising are those for iron transport. They are vital for virulence and survival of bacteria in the infected host, where iron depletion is a defense mechanism against invading pathogens. We synthesized biomimetic siderophores as shuttle vectors for active transport of antibiotics through the bacterial membrane. Structure activity relationship studies resulted in siderophore aminopenicillin conjugates that were highly active against Gram-negative pathogens which play a crucial role in destructive lung infections in cystic fibrosis patients and in severe nosocomial infections. The mechanism of action and the uptake of the compounds via specific iron siderophore transport routes were demonstrated. The novel conjugates were active against systemic Pseudomonas aeruginosa infections in mice with ED(50) values comparable to the quinolone ofloxacin and show low toxicity.

Keywords

Animals
Anti-Bacterial Agents/administration & dosage/adverse effects/chemistry/therapeutic use
Drug Delivery Systems/methods
Enterobactin/chemistry
Humans
Mice
Molecular Structure
Ofloxacin/administration & dosage/therapeutic use
Pseudomonas Infections/drug therapy
Pseudomonas aeruginosa/drug effects
Siderophores/chemistry
Structure-Activity Relationship

UNIGE affiliation entities

Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

Citation (ISO format)

MÖLLMANN, Ute et al. Siderophores as drug delivery agents: application of the ‘Trojan Horse’ strategy. In: BioMetals, 2009, vol. 22, n° 4, p. 615–624. doi: 10.1007/s10534-009-9219-2

Article (Published version)

Identifiers

PID : unige:5428
DOI : 10.1007/s10534-009-9219-2
PMID : 19214755

Additional URL for this publication

http://www.springerlink.com/content/a236922774127561/

Journal ISSN

0966-0844

644views

0downloads

Creation

16/03/2010 11:27:00

First validation

16/03/2010 11:27:00

Update

14/03/2023 15:25:04

Status update

14/03/2023 15:25:04

Last indexation

29/10/2024 13:05:40

Siderophores as drug delivery agents: application of the "Trojan Horse" strategy

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

Citation (ISO format)

Main files (1)

Identifiers

Additional URL for this publication

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation