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Tytuł pozycji:

Pegylated LyeTx I-b peptide is effective against carbapenem-resistant Acinetobacter baumannii in an in vivo model of pneumonia and shows reduced toxicity.

Tytuł:
Pegylated LyeTx I-b peptide is effective against carbapenem-resistant Acinetobacter baumannii in an in vivo model of pneumonia and shows reduced toxicity.
Autorzy:
César Moreira Brito J; Programa de Inovação Tecnológica e Biofarmacêutica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil; Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil. Electronic address: .
Gustavo Lima W; Laboratório de Radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Campus Pampulha, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Magalhães Resende J; Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Cristina Sampaio de Assis D; Escola de Veterinária, Departamento de Inspeção Sanitária, Campus Pampulha, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
Boff D; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Nascimento Cardoso V; Laboratório de Radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Campus Pampulha, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Almeida Amaral F; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Maria Souza-Fagundes E; Programa de Inovação Tecnológica e Biofarmacêutica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
Odília Antunes Fernandes S; Laboratório de Radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Campus Pampulha, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Elena de Lima M; Programa de Inovação Tecnológica e Biofarmacêutica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil; Faculdade Santa Casa de Belo Horizonte: Programa de Pós-Graduação em Medicina-Biomedicina, Belo Horizonte, Minas Gerais, Brazil. Electronic address: .
Źródło:
International journal of pharmaceutics [Int J Pharm] 2021 Nov 20; Vol. 609, pp. 121156. Date of Electronic Publication: 2021 Oct 06.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
MeSH Terms:
Acinetobacter baumannii*
Antimicrobial Cationic Peptides*
Peptide Fragments*/pharmacology
Pneumonia*
Animals ; Carbapenems ; Drug Resistance, Bacterial ; Drug Synergism ; Gentamicins/pharmacology ; HEK293 Cells ; Humans ; Mice ; Microbial Sensitivity Tests ; Peptides ; Polyethylene Glycols ; Receptors for Activated C Kinase
Contributed Indexing:
Keywords: Acinetobacter baumannii; Antimicrobial Peptide; LyeTx I-b; Pneumonia, PEGylation
Substance Nomenclature:
0 (Antimicrobial Cationic Peptides)
0 (Carbapenems)
0 (Gentamicins)
0 (LyeTx I protein, Lycosa erythrognatha)
0 (Peptide Fragments)
0 (Peptides)
0 (Receptors for Activated C Kinase)
3WJQ0SDW1A (Polyethylene Glycols)
Entry Date(s):
Date Created: 20211008 Date Completed: 20211109 Latest Revision: 20220531
Update Code:
20240104
DOI:
10.1016/j.ijpharm.2021.121156
PMID:
34624440
Czasopismo naukowe
The World Health Organization (WHO) has been warning about the importance of developing new drugs against superbugs. Antimicrobial peptides are an alternative in this context, most of them being involved in innate immunity, acting in various ways, and some even showing synergism with commercial antimicrobial agents. LyeTx I-b is a synthetic peptide derived from native LyeTx I, originally isolated from Lycosa erythrognatha spider venom. Although LyeTx I-b is active against several multidrug-resistant bacteria, it shows some hemolytic and cytotoxic effects. To overcome this hindrance, in the present study we PEGylated LyeTx I-b and evaluated its toxicity and in vitro and in vivo activities on pneumonia caused by multi-resistant Acinetobacter baumannii. PEGylated LyeTx I-b (LyeTx I-bPEG) maintained the same MIC value as the non- PEGylated peptide, showed anti-biofilm activity, synergistic effect with commercial antimicrobial agents, and did not induce resistance. Moreover, in vivo experiments showed its activity against pneumonia. Additionally, LyeTx I-bPEG reduced hemolysis up to 10 times, was approximately 2 times less cytotoxic to HEK-293 cells and 4 times less toxic to mice in acute toxicity models, compared to LyeTx I-b. Our results show LyeTx I-bPEG as a promising antimicrobial candidate, significantly active against pneumonia caused by multidrug-resistant A. baumannii.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

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