Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections.
Pathogenic microbes must acquire essential nutrients, including iron, from the host in order to proliferate and cause infections. Iron sequestration is an ancient host antimicrobial strategy. Thus, enhancing iron sequestration is a promising, novel anti-infective strategy. Unfortunately, small molecule iron chelators have proven difficult to develop as anti-infective treatments, in part due to unacceptable toxicities. Iron sequestration in mammals is predominantly mediated by the transferrin family of iron-binding proteins. In this review, we explore the possibility of administering supraphysiological levels of exogenous transferrin as an iron sequestering therapy for infections, which could overcome some of the problems associated with small molecule chelation. Recent studies suggest that transferrin delivery may represent a promising approach to augment both natural resistance and traditional antibiotic therapy.
Department of Molecular Microbiology & Immunology, Keck School of Medicine at the University of Southern California (USC), Los Angeles, CA, United States. Electronic address: kbruhn@usc.edu.
Kevin W
KW
Bruhn
Department of Medicine, Keck School of Medicine at USC, Los Angeles, United States.
Brad
B
Spellberg
D000818:Animals; D000890:Anti-Infective Agents; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D009181:Mycoses / Q000188:drug therapy* / Q000378:metabolism; D014168:Transferrin / Q000494:pharmacology / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D007502:Iron Chelating Agents; D014168:Transferrin; D007501:Iron