New antimicrobial peptide active against Gram-positive pathogens.
OBJECTIVE
Human and animal cystatins have been shown to inhibit the replication of certain viruses and bacteria, though it is not directly demonstrated that the effects are due to protease inhibitory capacity of the cystatins. We report antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(N(alpha)-benzyloxycarbonyl-arginyl-leucylamido)-1-[(E)-cinnamoylamido]-3- methylbutane, structurally based upon the aminoterminal segment of the inhibitory centre of the human cysteine protease inhibitor, cystatin C.


METHODS
Clinical isolates of group A, B, C and G streptococci were collected. The antibacterial activity of Cystapep 1 derivative was tested by agar well diffusion method.


RESULTS
Cystapep 1, displayed antibacterial activity against several clinically important Gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 microg/ml for both Staphylococcus aureus and Streptococcus pyogenes. In radial agar diffusion assays, groups A, B, C and G streptococci as well as staphylococci were generally susceptible to the action of Cystapep 1, whereas pneumococci and enterococci were less susceptible. No activity against Gram-negative bacteria was observed.


CONCLUSIONS
Cystapep 1 also showed high activity against methicillin-resistant Staph. aureus (MRSA) and multi-antibiotic resistant coagulase negative staphylococci (CNS), suggesting its mechanism of action to be different from most currently used antibiotics.
Jasir
A
A
Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden. aftab.jasir@mmb.lu.se
Kasprzykowski
F
F
Lindström
V
V
Schalén
C
C
Grubb
A
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests
C481042:2-(N(alpha)-benzyloxycarbonyl-arginyl-leucylamido)-1-(cinnamoylamido)-3-methylbutane; D000900:Anti-Bacterial Agents; D004151:Dipeptides