The antimicrobial peptide BMAP-28 reduces lethality in mouse models of staphylococcal sepsis

Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Cristina Bergnach, Fiorenza Orlando, Giuseppina D'Amato, Federico Mocchegiani, Carmela Silvestri, Maria Simona Del Prete, Barbara Skerlavaj, Vittorio Saba, Margherita Zanetti, Giorgio Scalise

Research output: Contribution to journalArticle

Abstract

Objective: A mouse model of staphylococcal sepsis was used to compare the efficacy of the bovine antimicrobial peptide BMAP-28, a compound of the cathelicidin family, with that of conventional antibiotics. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory in a university hospital. Subjects: BALB/c male mice. Interventions: BALB/c mice were injected intravenously with 2.0 × 106 colony-forming units of live Staphylococcus aureus ATCC 25923 or with 5.0 × 108 heat-killed cells of the same strain. All animals were randomized to receive intravenously isotonic sodium chloride solution, 2 mg/kg BMAP-28, 7 mg/kg imipenem, 7 mg/kg vancomycin, 7 mg/kg clindamycin, and 7 mg/kg clarithromycin immediately and at 6 hrs after bacterial challenge. Measurements and Main Results: Lethality, quantitative blood cultures, and detection of tumor necrosis factor-α and interleukin-6 plasma levels. In the experiments performed with five bacteria, all compounds reduced lethality rates and bacterial growth compared with controls. Imipenem and vancomycin exhibited the highest efficacy on these main outcome measures. In the experiments performed using heat-killed organisms, only BMAP-28 demonstrated significant efficacy on lethality rates, tumor necrosis factor-α, and interleukin-6 plasma levels compared with controls. Conclusion: These results highlight the capacity of BMAP-28 to reduce the effects of components of the bacterial cells and suggest that it may be beneficial in the treatment of severe staphylococcal infections in concert with other antimicrobial agents.

Original languageEnglish
Pages (from-to)2485-2490
Number of pages6
JournalCritical Care Medicine
Volume32
Issue number12
DOIs
Publication statusPublished - Dec 2004

Keywords

  • Antimicrobial peptide
  • BMAP-28
  • Cathelicidins
  • Septic shock
  • Staphylococcal sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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  • Cite this

    Giacometti, A., Cirioni, O., Ghiselli, R., Bergnach, C., Orlando, F., D'Amato, G., Mocchegiani, F., Silvestri, C., Del Prete, M. S., Skerlavaj, B., Saba, V., Zanetti, M., & Scalise, G. (2004). The antimicrobial peptide BMAP-28 reduces lethality in mouse models of staphylococcal sepsis. Critical Care Medicine, 32(12), 2485-2490. https://doi.org/10.1097/01.CCM.0000148221.09704.22