Isomerization of an antimicrobial peptide broadens antimicrobial spectrum to gram-positive bacterial pathogens.
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.
Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Siena, Italy.
Chiara
C
Falciani
Luisa
L
Lozzi
Simona
S
Pollini
Vincenzo
V
Luca
Veronica
V
Carnicelli
Jlenia
J
Brunetti
Barbara
B
Lelli
Stefano
S
Bindi
Silvia
S
Scali
Antonio
A
Di Giulio
Gian Maria
GM
Rossolini
Maria Luisa
ML
Mangoni
Luisa
L
Bracci
Alessandro
A
Pini
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms; D007536:Isomerism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013212:Staphylococcus epidermidis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D010455:Peptides