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New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci

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Abstract:

Jasir A, Kasprzykowski F, Kasprzykowska R, Lindström V, Schalén C, Grubb A. New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci. APMIS 2003;111:–.

We describe the synthesis and antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(Nα-benzyloxycarbonyl-arginyl-leucylamido-1-[(E)-cinnamoylamido]-3-methylbutane, structurally based upon the inhibitory centre of the human cysteine protease inhibitor, cystatin C. The derivative, here called Cystapep 1, displayed antibacterial activity against several clinically important gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 μg/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. Cystapep 1 also showed high activity against methicillin-resistant S. aureus (MRSA) and multiantibiotic-resistant coagulase-negative staphylococci (CNS), suggesting that its mechanism of action differs from those of most currently used antibiotics.

Keywords: Cystatin C; Staphylococcus aureus; Streptococcus pyogenes; antimicrobial peptide; gram-positive pathogens

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2003.t01-1-apm1111102.x

Affiliations: 1: Department of Clinical Chemistry, University Hospital, Lund, Sweden 2: Department of Chemistry, University of Gdansk, Gdansk, Poland 3: Department of Medical Microbiology, Dermatology, and Infection, University Hospital, Lund, Sweden

Publication date: November 1, 2003

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