Dermaseptins From Phyllomedusa oreades and Phyllomedusa distincta: Antimicrobial Activity against Bovine Mastitic Bacteria Strains and Toxicity in Mice

Leite, J.R.S.A.^{1,2,3,*, Brand, G.D.1,4}, Kückelhaus, S.A.S.^5,6, Silva, L.P.⁷, Araújo, A.LT.³ and Bloch Jr, C.¹

1 Laboratory of Mass Spectrometry, EMBRAPA Recourses Genetics and Biotechnology, Brasilia, Brasil; 2 Depart. Cell Biology, University of Brasilia, Brasilia, Brasil; 3 Clinical Analyses SABIN Laboratory, Brasília, Brasil; 4 Depart. Physiology, University of Brasilia; 5 College JK, Brasília, Brasil; 6 Depart. Medicine, University of Brasilia; 7 Dept. Genetics and Morfology, University of Brasilia. 

Amphibian skin is a rich source of biologically active compounds known to have diverse physiological and defensive functions. In addition to the miriad of pharmacologically active hormone analogs, skin secretions contain a broad spectrum of antimicrobial peptides. Dermaseptins are a class of antimicrobial peptides present in tree frogs of the Phyllomedusa genus. They are cationic molecules of 24-34 residues that permeabilize the membrane of Gram-positive and Gram-negative bacteria, yeasts, and filamentous fungi, showing little or no hemolytic activity. This work reports the synthesis, antimicrobial activities, citotoxicity in peritoneal macrophages and effect on blood and liver biochemical parameters of dermaseptins from the skin secretion of Phyllomedusaoreades (DS 01) and P. distincta (DD L). The range of MICs for DS 01 against clinical isolates of Staphylococcus aureus, Klebsiellasp, Streptococcus agalactiae and S. dysgalactiae were, 4-32 mg/mL. DD L demonstrated high citotoxicity compared to DS 01 for peritoneal macrophages. However, DD L and DS 01 presented low toxicity to blood cells (erythrocytes and white blood cells) after endovenous treatment (5 and 10 mg/Kg). Mice Liver and plasma (n=3) biochemical and inorganic parameters were determined by spectrophotometry (ADVIA 1650 Chemistry System, Bayer A/S, Lyngby, Denmark). DS 01 presented low diference compared to the control (mice trated with saline solution) in albumin, bile acids, HDL, iron, triglyceride, creatinine, cholesterol, glucose and phosphate inorganic concentrations. The experimental and control group were compared using a t-test. Differences were not considered statistically significant for P0.05. Overall, the data suggests that DS 01 could be useful in the treatment of infections, including those caused by multidrug-resistant bacteria.

Supported By: Laboratório SABIN de Análises Clínicas, EMBRAPA Recursos Genéticos e Biotecnologia, CNPq

Correspondence to: jrleite@cenargen.embrapa.br