title: Targeted Delivery of Amoxicillin to C. trachomatis by the Transferrin Iron Acquisition Pathway.
abstract: Weak intracellular penetration of antibiotics makes some infections difficult to treat. The Trojan horse strategy for targeted drug delivery is among the interesting routes being explored to overcome this therapeutic difficulty. Chlamydia trachomatis, as an obligate intracellular human pathogen, is responsible for both trachoma and sexually transmitted diseases. Chlamydia develops in a vacuole and is therefore protected by four membranes (plasma membrane, bacterial inclusion membrane, and bacterial membranes). In this work, the iron-transport protein, human serum-transferrin, was used as a Trojan horse for antibiotic delivery into the bacterial vacuole. Amoxicillin was grafted onto transferrin. The transferrin-amoxicillin construct was characterized by mass spectrometry and absorption spectroscopy. Its affinity for transferrin receptor 1, determined by fluorescence emission titration [KaffTf-amox = (1.3 ± 1.0) x 108], is very close to that of transferrin [4.3 x 108]. Transmission electron and confocal microscopies showed a co-localization of transferrin with the bacteria in the vacuole and were also used to evaluate the antibiotic capability of the construct. It is significantly more effective than amoxicillin alone. These promising results demonstrate targeted delivery of amoxicillin to suppress Chlamydia and are of interest for Chlamydiaceae and maybe other intracellular bacteria therapies.
authors.affiliation: ITODYS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, Université Paris Diderot, Sorbonne Paris Cité, CNRS-UMR 7086, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Jun
authors.initials: J
authors.lastname: Hai
authors.affiliation: ITODYS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, Université Paris Diderot, Sorbonne Paris Cité, CNRS-UMR 7086, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Nawal
authors.initials: N
authors.lastname: Serradji
authors.affiliation: ITODYS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, Université Paris Diderot, Sorbonne Paris Cité, CNRS-UMR 7086, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Mouton
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS-UMR 9197, 1 avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Redeker
authors.affiliation: Service d'Identification et de Caractérisation des Protéines, CNRS-UMR 9198, 1 avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: David
authors.initials: D
authors.lastname: Cornu
authors.affiliation: ITODYS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, Université Paris Diderot, Sorbonne Paris Cité, CNRS-UMR 7086, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: El Hage Chahine
authors.affiliation: UMR 1149 Inserm, Université Paris Diderot, Sorbonne Paris Cité, ERL-CNRS 8252, Faculté de Médecine, site Bichat, 16 rue Henri Huchard, 75018 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Verbeke
authors.affiliation: ITODYS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, Université Paris Diderot, Sorbonne Paris Cité, CNRS-UMR 7086, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Miryana
authors.initials: M
authors.lastname: Hémadi
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002690:Chlamydia Infections / Q000188:drug therapy; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D007501:Iron / Q000378:metabolism*; D014141:Trachoma / Q000188:drug therapy; D014168:Transferrin / Q000378:metabolism*; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D014168:Transferrin; D000658:Amoxicillin; D007501:Iron