期刊
JOURNAL OF INFECTIOUS DISEASES
卷 210, 期 2, 页码 254-264出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu049
关键词
transferrin; iron; Staphylococcus aureus; Acinetobacter baumannii; Candida albicans; in vivo treatment
资金
- NIH/NIAID [R01 AI081719, R21 AI101750, R21 AI101492, R21 AI107233, S10RR026742]
- Los Angeles Biomedical Research Institute Seed Grant
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.
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