Author(s): Santos-Filho, Norival A. [UNESP] ; Fernandes, Rafaela S. ; Sgardioli, Bruna F. ; Ramos, Matheus A. S. [UNESP] ; Piccoli, Julia P. [UNESP] ; Camargo, Ilana L. B. C. ; Bauab, Tais M. [UNESP] ; Cilli, Eduardo M. [UNESP]
Date: 2018
Persistent ID: http://hdl.handle.net/11449/179358
Origin: Oasisbr
Subject(s): (P-BthTX-I)2; Antimicrobial peptides; Biofilm; Multidrug-resistant bacteria
Made available in DSpace on 2018-12-11T17:34:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-01
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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-Lys12/Lys13-(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-Lys12/Lys13-(p-BthTX-I)2 were evaluated against a variety of bacteria, including multidrug-resistant strains. Des-Lys12/Lys13-(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.
Instituto de Química Universidade Estadual Paulista (UNESP)
Instituto de Física de São Carlos USP-Universidade de São Paulo
Faculdade de Ciências Farmaceûticas Universidade Estadual Paulista (UNESP)
Instituto de Química Universidade Estadual Paulista (UNESP)
Faculdade de Ciências Farmaceûticas Universidade Estadual Paulista (UNESP)
FAPESP: #2014/05538-1
