Isomerization of an Antimicrobial Peptide Broadens Antimicrobial Spectrum to Gram-Positive Bacterial Pathogens

Chiara Falciani, Luisa Lozzi, Simona Pollini, Vincenzo Luca, Veronica Carnicelli, Jlenia Brunetti, Barbara Lelli, Stefano Bindi, Silvia Scali, Antonio Di Giulio, Gian Maria Rossolini, Maria Luisa Mangoni, Luisa Bracci, Alessandro Pini

Research output: Contribution to journalArticlepeer-review

Abstract

The branched M33 antimicrobial peptide was previously shown to be very active against Gram-negative bacterial pathogens, including multidrug-resistant strains. In an attempt to produce back-up molecules, we synthesized an M33 peptide isomer consisting of D-aminoacids (M33-D). This isomeric version showed 4 to 16-fold higher activity against Gram-positive pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, than the original peptide, while retaining strong activity against Gram-negative bacteria. The antimicrobial activity of both peptides was influenced by their differential sensitivity to bacterial proteases. The better activity shown by M33-D against S. aureus compared to M33-L was confirmed in biofilm eradication experiments where M33-L showed 12% activity with respect to M33-D, and in vivo models where Balb-c mice infected with S. aureus showed 100% and 0% survival when treated with M33-D and M33-L, respectively. M33-D appears to be an interesting candidate for the development of novel broad-spectrum antimicrobials active against bacterial pathogens of clinical importance.

Original languageEnglish
Article numbere46259
JournalPLoS One
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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