Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved

Eszter Ostorhazi, Marianna Csilla Holub, Ferenc Rozgonyi, Ferenc Harmos, Marco Cassone, John D. Wade, Laszlo Otvos

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Although the designer proline-rich antimicrobial peptide A3-APO has only modest activity against Escherichia coli and Acinetobacter baumannii in vitro, in mouse models of systemic and wound infections it shows superior efficacy compared with conventional antibiotics. In this study, the efficacy of A3-APO in several additional mouse models was investigated, including Staphylococcus aureus wound infection, mixed Klebsiella pneumoniae-A. baumannii-Proteus mirabilis wound infection and K. pneumoniae lung infection, mimicking blast wound infections, foot ulcers and ventilator-induced nosocomial infections, respectively. Whilst the peptide practically did not kill the strains in vitro, when administered intramuscularly or as an aerosol it significantly improved mouse survival and reduced bacterial counts at the infection site and in blood. In the lung infection study, the blood bacterial counts following A3-APO treatment were as low as after treatment with colistin and were lower than after treatment with imipenem or amikacin. The wounds of treated animals, unlike their untreated counterparts, lacked pus and signs of inflammation. In human peripheral blood mononuclear cells, A3-APO upregulated the expression of the anti-inflammatory cytokines interleukin-4 and interleukin-10 by four- to six-fold. One of the mechanisms mediating the in vivo protective effects might be the prevention of inflammation around bacterial infiltration.

Original languageEnglish
Pages (from-to)480-484
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume37
Issue number5
DOIs
Publication statusPublished - May 1 2011

Keywords

  • Aerosol
  • Anti-inflammatory
  • Bacterial counts
  • Enterobacteriaceae
  • Intramuscular
  • MRSA
  • Peptide antibiotic
  • Survival rate

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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