Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.bbagen.2021.129937 http://hdl.handle.net/11449/228962 |
Resumo: | Background: Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus. Methods: A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations. Results: RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces. Conclusions: RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application. General significance: These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces. |
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Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranesAntimicrobial peptidesBacteriaCandidaMembrane selectivityBackground: Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus. Methods: A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations. Results: RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces. Conclusions: RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application. General significance: These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces.Financiadora de Estudos e ProjetosConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de Mato Grosso do SulUniversidade Federal da Grande DouradosOncolytic Anticancer DrugsInstituto de Química Departamento de Bioquímica e Química Tecnológica Universidade Estadual Paulista Júlio de Mesquita FilhoInstituto de Biociências Universidade Federal de Mato Grosso do SulUniversidade Estadual do Norte FluminenseCentro de Análises Proteômicas e Bioquímicas Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de BrasíliaS-inova Biotech Programa de Pós-Graduação em Biotecnologia Universidade Católica Dom BoscoInstituto de Química Departamento de Bioquímica e Química Tecnológica Universidade Estadual Paulista Júlio de Mesquita FilhoCNPq: 302175/2020-2CNPq: 305679/2016-3CNPq: 426912/2018-7CNPq: 430694/2016-4Universidade Federal de Mato Grosso do Sul (UFMS)Universidade Federal da Grande DouradosOncolytic Anticancer DrugsUniversidade Estadual Paulista (UNESP)Universidade Estadual do Norte FluminenseUniversidade Católica de BrasíliaUniversidade Católica Dom BoscoAlmeida, Claudiane V.de Oliveira, Caio F.R.dos Santos, Edson L.dos Santos, Helder F.Júnior, Edson C. [UNESP]Marchetto, Reinaldo [UNESP]da Cruz, Leticia A.Ferreira, Alda Maria T.Gomes, Valdirene M.Taveira, Gabriel B.Costa, Bruna O.Franco, Octávio L.Cardoso, Marlon H.Macedo, Maria Lígia R.2022-04-29T08:29:35Z2022-04-29T08:29:35Z2021-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.bbagen.2021.129937Biochimica et Biophysica Acta - General Subjects, v. 1865, n. 9, 2021.1872-80060304-4165http://hdl.handle.net/11449/22896210.1016/j.bbagen.2021.1299372-s2.0-85107702211Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiochimica et Biophysica Acta - General Subjectsinfo:eu-repo/semantics/openAccess2022-04-29T08:29:35Zoai:repositorio.unesp.br:11449/228962Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-29T08:29:35Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
title |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
spellingShingle |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes Almeida, Claudiane V. Antimicrobial peptides Bacteria Candida Membrane selectivity |
title_short |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
title_full |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
title_fullStr |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
title_full_unstemmed |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
title_sort |
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes |
author |
Almeida, Claudiane V. |
author_facet |
Almeida, Claudiane V. de Oliveira, Caio F.R. dos Santos, Edson L. dos Santos, Helder F. Júnior, Edson C. [UNESP] Marchetto, Reinaldo [UNESP] da Cruz, Leticia A. Ferreira, Alda Maria T. Gomes, Valdirene M. Taveira, Gabriel B. Costa, Bruna O. Franco, Octávio L. Cardoso, Marlon H. Macedo, Maria Lígia R. |
author_role |
author |
author2 |
de Oliveira, Caio F.R. dos Santos, Edson L. dos Santos, Helder F. Júnior, Edson C. [UNESP] Marchetto, Reinaldo [UNESP] da Cruz, Leticia A. Ferreira, Alda Maria T. Gomes, Valdirene M. Taveira, Gabriel B. Costa, Bruna O. Franco, Octávio L. Cardoso, Marlon H. Macedo, Maria Lígia R. |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Mato Grosso do Sul (UFMS) Universidade Federal da Grande Dourados Oncolytic Anticancer Drugs Universidade Estadual Paulista (UNESP) Universidade Estadual do Norte Fluminense Universidade Católica de Brasília Universidade Católica Dom Bosco |
dc.contributor.author.fl_str_mv |
Almeida, Claudiane V. de Oliveira, Caio F.R. dos Santos, Edson L. dos Santos, Helder F. Júnior, Edson C. [UNESP] Marchetto, Reinaldo [UNESP] da Cruz, Leticia A. Ferreira, Alda Maria T. Gomes, Valdirene M. Taveira, Gabriel B. Costa, Bruna O. Franco, Octávio L. Cardoso, Marlon H. Macedo, Maria Lígia R. |
dc.subject.por.fl_str_mv |
Antimicrobial peptides Bacteria Candida Membrane selectivity |
topic |
Antimicrobial peptides Bacteria Candida Membrane selectivity |
description |
Background: Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus. Methods: A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations. Results: RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces. Conclusions: RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application. General significance: These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-09-01 2022-04-29T08:29:35Z 2022-04-29T08:29:35Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.bbagen.2021.129937 Biochimica et Biophysica Acta - General Subjects, v. 1865, n. 9, 2021. 1872-8006 0304-4165 http://hdl.handle.net/11449/228962 10.1016/j.bbagen.2021.129937 2-s2.0-85107702211 |
url |
http://dx.doi.org/10.1016/j.bbagen.2021.129937 http://hdl.handle.net/11449/228962 |
identifier_str_mv |
Biochimica et Biophysica Acta - General Subjects, v. 1865, n. 9, 2021. 1872-8006 0304-4165 10.1016/j.bbagen.2021.129937 2-s2.0-85107702211 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biochimica et Biophysica Acta - General Subjects |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799965283044032512 |