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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Molecules; v. 22, n. 11 NOV 2017.
Web of Science Citations: 2
Abstract

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)

FAPESP's process: 14/05538-1 - Synthesis, characterization, study of action mechanism and analysis of different release methods of pBthTX-I, in its monomeric and dimeric forms
Grantee:Norival Alves Santos Filho
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC