Transferrin iron starvation therapy for lethal bacterial and fungal infections.

Lin L, Pantapalangkoor P, Tan B, Bruhn KW, Ho T, Nielsen T, Skaar EP, Zhang Y, Bai R, Wang A, Doherty TM, Spellberg B
J Infect Dis. 2014 210 (2): 254-64

PMID: 24446527 · PMCID: PMC4092247 · DOI:10.1093/infdis/jiu049

New strategies to treat antibiotic-resistant infections are urgently needed. We serendipitously discovered that stem cell conditioned media possessed broad antimicrobial properties. Biochemical, functional, and genetic assays confirmed that the antimicrobial effect was mediated by supra-physiological concentrations of transferrin. Human transferrin inhibited growth of gram-positive (Staphylococcus aureus), gram-negative (Acinetobacter baumannii), and fungal (Candida albicans) pathogens by sequestering iron and disrupting membrane potential. Serial passage in subtherapeutic transferrin concentrations resulted in no emergence of resistance. Infected mice treated with intravenous human transferrin had improved survival and reduced microbial burden. Finally, adjunctive transferrin reduced the emergence of rifampin-resistant mutants of S. aureus in infected mice treated with rifampin. Transferrin is a promising, novel antimicrobial agent that merits clinical investigation. These results provide proof of principle that bacterial infections can be treated in vivo by attacking host targets (ie, trace metal availability) rather than microbial targets.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

MeSH Terms (16)

Acinetobacter baumannii Acinetobacter Infections Animals Candida albicans Candidiasis Cells, Cultured Humans Iron Male Mice Mice, Inbred BALB C Mice, Inbred C3H Staphylococcal Infections Staphylococcus aureus Transferrin Treatment Outcome

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