Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria

J Antimicrob Chemother. 2019 Sep 1;74(9):2631-2639. doi: 10.1093/jac/dkz225.


Background: New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens-including Gram-negative bacteria-to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.

Objectives: To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.

Methods: The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time-kill assay and assays for the selection of resistant mutants.

Results: We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time-kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.

Conclusions: These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / therapeutic use*
  • Apoproteins / pharmacology*
  • Ciprofloxacin / therapeutic use
  • Drug Resistance, Bacterial / drug effects*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Meropenem / therapeutic use
  • Microbial Sensitivity Tests
  • Mutation
  • Transferrin / pharmacology*


  • Anti-Bacterial Agents
  • Apoproteins
  • Transferrin
  • apotransferrin
  • Ciprofloxacin
  • Meropenem