Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria
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...
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doaj-a3ac547788894b689642a4d8338205472020-11-24T20:41:33ZengMDPI AGMolecules1420-30492017-11-012211189810.3390/molecules22111898molecules22111898Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant BacteriaNorival A. Santos-Filho0Rafaela S. Fernandes1Bruna F. Sgardioli2Matheus A. S. Ramos3Julia P. Piccoli4Ilana L. B. C. Camargo5Tais M. Bauab6Eduardo M. Cilli7Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-060, BrazilInstituto de Física de São Carlos, USP—Universidade de São Paulo, São Carlos-SP 13563-120, BrazilInstituto de Física de São Carlos, USP—Universidade de São Paulo, São Carlos-SP 13563-120, BrazilFaculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-903, BrazilInstituto de Química, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-060, BrazilInstituto de Física de São Carlos, USP—Universidade de São Paulo, São Carlos-SP 13563-120, BrazilFaculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-903, BrazilInstituto de Química, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-060, BrazilAntimicrobial 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.https://www.mdpi.com/1420-3049/22/11/1898(p-BthTX-I)2multidrug-resistant bacteriabiofilmantimicrobial peptides |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Norival A. Santos-Filho Rafaela S. Fernandes Bruna F. Sgardioli Matheus A. S. Ramos Julia P. Piccoli Ilana L. B. C. Camargo Tais M. Bauab Eduardo M. Cilli |
spellingShingle |
Norival A. Santos-Filho Rafaela S. Fernandes Bruna F. Sgardioli Matheus A. S. Ramos Julia P. Piccoli Ilana L. B. C. Camargo Tais M. Bauab Eduardo M. Cilli Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria Molecules (p-BthTX-I)2 multidrug-resistant bacteria biofilm antimicrobial peptides |
author_facet |
Norival A. Santos-Filho Rafaela S. Fernandes Bruna F. Sgardioli Matheus A. S. Ramos Julia P. Piccoli Ilana L. B. C. Camargo Tais M. Bauab Eduardo M. Cilli |
author_sort |
Norival A. Santos-Filho |
title |
Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria |
title_short |
Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria |
title_full |
Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria |
title_fullStr |
Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria |
title_full_unstemmed |
Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)2 and Its Serum Degradation Product against Multidrug-Resistant Bacteria |
title_sort |
antibacterial activity of the non-cytotoxic peptide (p-bthtx-i)2 and its serum degradation product against multidrug-resistant bacteria |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-11-01 |
description |
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. |
topic |
(p-BthTX-I)2 multidrug-resistant bacteria biofilm antimicrobial peptides |
url |
https://www.mdpi.com/1420-3049/22/11/1898 |
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