BioMetals

, 22:61

Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents

  • Marvin J. Miller
  • Helen Zhu
  • Yanping Xu
  • Chunrui Wu
  • Andrew J. Walz
  • Anne Vergne
  • John M. Roosenberg
  • Garrett Moraski
  • Albert A. Minnick
  • Julia McKee-Dolence
  • Jingdan Hu
  • Kelley Fennell
  • E. Kurt Dolence
  • Li Dong
  • Scott Franzblau
  • Francois Malouin
  • Ute Möllmann
Article

DOI: 10.1007/s10534-008-9185-0

Cite this article as:
Miller, M.J., Zhu, H., Xu, Y. et al. Biometals (2009) 22: 61. doi:10.1007/s10534-008-9185-0

Abstract

Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the “microbial war”, extensive interdisciplinary research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase) and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery (“Trojan Horse” antibiotics) and induction of iron limitation/starvation (Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of novel potent and selective anticancer agents are also described.

Keywords

SiderophoresDrug conjugatesAntibioticsMycobactinsAntituberculosis agentsAnticancer agents

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Marvin J. Miller
    • 1
  • Helen Zhu
    • 1
  • Yanping Xu
    • 1
  • Chunrui Wu
    • 1
  • Andrew J. Walz
    • 1
  • Anne Vergne
    • 1
  • John M. Roosenberg
    • 1
  • Garrett Moraski
    • 1
  • Albert A. Minnick
    • 1
  • Julia McKee-Dolence
    • 1
  • Jingdan Hu
    • 1
  • Kelley Fennell
    • 1
  • E. Kurt Dolence
    • 1
  • Li Dong
    • 1
  • Scott Franzblau
    • 2
  • Francois Malouin
    • 3
  • Ute Möllmann
    • 4
  1. 1.Department of Chemistry and BiochemistryUniversity of Notre DameNotre DameUSA
  2. 2.College of PharmacyUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Département de BiologieUniversité de SherbrookeSherbrookeCanada
  4. 4.Leibniz Institute for Natural Product Research and Infection Biology e.V. Hans Knöll InstituteJenaGermany