Targeted Delivery of Amoxicillin to C. trachomatis by the Transferrin Iron Acquisition Pathway

PLoS One. 2016 Feb 26;11(2):e0150031. doi: 10.1371/journal.pone.0150031. eCollection 2016.

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.

MeSH terms

  • Amoxicillin / administration & dosage*
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / therapeutic use
  • Chlamydia Infections / drug therapy
  • Chlamydia trachomatis / drug effects*
  • Chlamydia trachomatis / metabolism
  • Drug Delivery Systems
  • Humans
  • Iron / metabolism*
  • Trachoma / drug therapy
  • Transferrin / metabolism*
  • Vacuoles / drug effects
  • Vacuoles / metabolism

Substances

  • Anti-Bacterial Agents
  • Transferrin
  • Amoxicillin
  • Iron

Grants and funding

The authors received no specific funding for this work.