New antimicrobial peptide active against Gram-positive pathogens.

BACKGROUND & OBJECTIVES: 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. INTERPRETATION & CONCLUSION: 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.

Induction of myocarditis in rabbits injected with group A streptococci.

BACKGROUND & OBJECTIVES: We have earlier proposed that group A streptococcal (GAS) immunoglobulin binding surface proteins (IgGBPs) might trigger anti-IgG production and immune complex formation leading to glomerulonephritis. In the present study, cardiac tissue material from rabbits injected with heat-killed GAS was investigated. METHODS: Rabbits were injected intravenously with 10(9) colony forming units of streptococci three times weekly for 8 wk. Cardiac tissue samples were obtained at different times and deposition of IgG, C3, TNF-alpha and IL-6 was studied. RESULTS: After 8 or more weeks of intravenous (iv) injections, minimal changes were seen in animals receiving an IgG non-binding GAS strain, type T27, whereas in those animals receiving either of two IgG binding GAS strains, types M1 or M22, strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3 were noted. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence streptococcal IgGBPs. INTERPRETATION & CONCLUSION: The present data supported a role of streptococcal IgGBPs in the induction of myocardial tissue injury by GAS.