Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)(2) and Its Serum Degradation Product against Multidrug-Resistant Bacteria

Autor(es)

Santos-Filho, Norival A. ^[1] ; Fernandes, Rafaela S. ^[2] ; Sgardioli, Bruna F. ^[2] ; Ramos, Matheus A. S. ^[3] ; Piccoli, Julia P. ^[1] ; Camargo, Ilana L. B. C. ^[2] ; Bauab, Tais M. ^[3] ; Cilli, Eduardo M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista UNESP, Inst Quim, BR-14800060 Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13563120 Sao Carlos, SP - Brazil

^[3] Univ Estadual Paulista UNESP, Fac Ciencias Farmaceut, BR-14800903 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 22, n. 11 NOV 2017.
• Citações Web of Science: 2

Resumo

Antimicrobial peptides can be used systemically, however, their susceptibility to proteases is a major obstacle in peptide-based therapeutic development. In the present study, the serum stability of p-BthTX-I (KKYRYHLKPFCKK) and (p-BthTX-I)(2), a p-BthTX-I disulfide-linked dimer, were analyzed by mass spectrometry and analytical high-performance liquid chromatography (HPLC). Antimicrobial activities were assessed by determining their minimum inhibitory concentrations (MIC) using cation-adjusted Mueller-Hinton broth. Furthermore, biofilm eradication and time-kill kinetics were performed. Our results showed that p-BthTX-I and (p-BthTX-I)(2) were completely degraded after 25 min. Mass spectrometry showed that the primary degradation product was a peptide that had lost four lysine residues on its C-terminus region (des-Lys(12)/Lys(13)-(p-BthTX-I)(2)), which was stable after 24 h of incubation. The antibacterial activities of the peptides p-BthTX-I, (p-BthTX-I)(2), and des-Lys(12)/Lys(13)-(p-BthTX-I)(2) were evaluated against a variety of bacteria, including multidrug-resistant strains. Des-Lys(12)/Lys(13)-(p-BthTX-I)(2) and (p-BthTX-I)(2) degraded Staphylococcus epidermidis biofilms. Additionally, both the peptides exhibited bactericidal activities against planktonic S. epidermidis in time-kill assays. The emergence of bacterial resistance to a variety of antibiotics used in clinics is the ultimate challenge for microbial infection control. Therefore, our results demonstrated that both peptides analyzed and the product of proteolysis obtained from (p-BthTX-I)(2) are promising prototypes as novel drugs to treat multidrug-resistant bacterial infections. (AU)

• Processo FAPESP: 14/05538-1 - Síntese, caracterização, estudo do mecanismo de ação e análise de métodos de liberação do peptídeo pBthTX-I, nas formas monoméricas e diméricas
• Beneficiário: Norival Alves Santos Filho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs