Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ

Autores
Sala, C.D.; Soler-Bistué, A.J.C.; Korprapun, L.; Zorreguieta, A.; Tolmasky, M.E.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
EGS (external guide sequence) technology is a promising approach to designing new antibiotics. EGSs are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. The ftsZ mRNA secondary structure was modeled and EGSs complementary to two regions with high probability of being suitable targets were designed. In vitro reactions showed that EGSs targeting these regions bound ftsZ mRNA and elicited RNase P-mediated cleavage of ftsZ mRNA. A recombinant plasmid, pEGSb1, coding for an EGS that targets region "b" under the control of the T7 promoter was generated. Upon introduction of this plasmid into Escherichia coli BL21(DE3)(pLysS) the transformant strain formed filaments when expression of the EGS was induced. Concomitantly, E. coli harboring pEGSb1 showed a modest but significant inhibition of growth when synthesis of the EGSb1 was induced. Our results indicate that EGS technology could be a viable strategy to generate new antimicrobials targeting ftsZ. © 2012 Sala et al.
Fil:Soler-Bistué, A.J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Zorreguieta, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Tolmasky, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fuente
PLoS ONE 2012;7(10)
Materia
messenger RNA
ribonuclease P
transfer RNA
article
bacterial cell
binding affinity
binding site
complex formation
controlled study
Escherichia coli
experimental design
external guide sequence technology
ftsZ gene
gene
gene targeting
gene technology
growth inhibition
in vitro study
mitosis inhibition
nonhuman
promoter region
protein secondary structure
recombinant plasmid
RNA binding
RNA cleavage
RNA structure
sequence analysis
Anti-Bacterial Agents
Bacterial Proteins
Base Sequence
Cell Division
Cytoskeletal Proteins
Drug Design
Electrophoretic Mobility Shift Assay
Escherichia coli
Microscopy, Confocal
Molecular Sequence Data
Nucleic Acid Conformation
Oligoribonucleotides, Antisense
Promoter Regions, Genetic
Ribonuclease P
RNA Cleavage
Terminator Regions, Genetic
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/2.5/ar
Repositorio
Biblioteca Digital (UBA-FCEN)
Institución
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identificador
paperaa:paper_19326203_v7_n10_p_Sala
Acceder
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oai_identifier_str paperaa:paper_19326203_v7_n10_p_Sala
network_acronym_str BDUBAFCEN
repository_id_str 1896
network_name_str Biblioteca Digital (UBA-FCEN)
spelling Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZSala, C.D.Soler-Bistué, A.J.C.Korprapun, L.Zorreguieta, A.Tolmasky, M.E.messenger RNAribonuclease Ptransfer RNAarticlebacterial cellbinding affinitybinding sitecomplex formationcontrolled studyEscherichia coliexperimental designexternal guide sequence technologyftsZ genegenegene targetinggene technologygrowth inhibitionin vitro studymitosis inhibitionnonhumanpromoter regionprotein secondary structurerecombinant plasmidRNA bindingRNA cleavageRNA structuresequence analysisAnti-Bacterial AgentsBacterial ProteinsBase SequenceCell DivisionCytoskeletal ProteinsDrug DesignElectrophoretic Mobility Shift AssayEscherichia coliMicroscopy, ConfocalMolecular Sequence DataNucleic Acid ConformationOligoribonucleotides, AntisensePromoter Regions, GeneticRibonuclease PRNA CleavageTerminator Regions, GeneticEGS (external guide sequence) technology is a promising approach to designing new antibiotics. EGSs are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. The ftsZ mRNA secondary structure was modeled and EGSs complementary to two regions with high probability of being suitable targets were designed. In vitro reactions showed that EGSs targeting these regions bound ftsZ mRNA and elicited RNase P-mediated cleavage of ftsZ mRNA. A recombinant plasmid, pEGSb1, coding for an EGS that targets region "b" under the control of the T7 promoter was generated. Upon introduction of this plasmid into Escherichia coli BL21(DE3)(pLysS) the transformant strain formed filaments when expression of the EGS was induced. Concomitantly, E. coli harboring pEGSb1 showed a modest but significant inhibition of growth when synthesis of the EGSb1 was induced. Our results indicate that EGS technology could be a viable strategy to generate new antimicrobials targeting ftsZ. © 2012 Sala et al.Fil:Soler-Bistué, A.J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Zorreguieta, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Tolmasky, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.2012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_SalaPLoS ONE 2012;7(10)reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-09-04T09:48:21Zpaperaa:paper_19326203_v7_n10_p_SalaInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-09-04 09:48:22.723Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse
dc.title.none.fl_str_mv Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
title Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
spellingShingle Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
Sala, C.D.
messenger RNA
ribonuclease P
transfer RNA
article
bacterial cell
binding affinity
binding site
complex formation
controlled study
Escherichia coli
experimental design
external guide sequence technology
ftsZ gene
gene
gene targeting
gene technology
growth inhibition
in vitro study
mitosis inhibition
nonhuman
promoter region
protein secondary structure
recombinant plasmid
RNA binding
RNA cleavage
RNA structure
sequence analysis
Anti-Bacterial Agents
Bacterial Proteins
Base Sequence
Cell Division
Cytoskeletal Proteins
Drug Design
Electrophoretic Mobility Shift Assay
Escherichia coli
Microscopy, Confocal
Molecular Sequence Data
Nucleic Acid Conformation
Oligoribonucleotides, Antisense
Promoter Regions, Genetic
Ribonuclease P
RNA Cleavage
Terminator Regions, Genetic
title_short Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
title_full Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
title_fullStr Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
title_full_unstemmed Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
title_sort Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
dc.creator.none.fl_str_mv Sala, C.D.
Soler-Bistué, A.J.C.
Korprapun, L.
Zorreguieta, A.
Tolmasky, M.E.
author Sala, C.D.
author_facet Sala, C.D.
Soler-Bistué, A.J.C.
Korprapun, L.
Zorreguieta, A.
Tolmasky, M.E.
author_role author
author2 Soler-Bistué, A.J.C.
Korprapun, L.
Zorreguieta, A.
Tolmasky, M.E.
author2_role author
author
author
author
dc.subject.none.fl_str_mv messenger RNA
ribonuclease P
transfer RNA
article
bacterial cell
binding affinity
binding site
complex formation
controlled study
Escherichia coli
experimental design
external guide sequence technology
ftsZ gene
gene
gene targeting
gene technology
growth inhibition
in vitro study
mitosis inhibition
nonhuman
promoter region
protein secondary structure
recombinant plasmid
RNA binding
RNA cleavage
RNA structure
sequence analysis
Anti-Bacterial Agents
Bacterial Proteins
Base Sequence
Cell Division
Cytoskeletal Proteins
Drug Design
Electrophoretic Mobility Shift Assay
Escherichia coli
Microscopy, Confocal
Molecular Sequence Data
Nucleic Acid Conformation
Oligoribonucleotides, Antisense
Promoter Regions, Genetic
Ribonuclease P
RNA Cleavage
Terminator Regions, Genetic
topic messenger RNA
ribonuclease P
transfer RNA
article
bacterial cell
binding affinity
binding site
complex formation
controlled study
Escherichia coli
experimental design
external guide sequence technology
ftsZ gene
gene
gene targeting
gene technology
growth inhibition
in vitro study
mitosis inhibition
nonhuman
promoter region
protein secondary structure
recombinant plasmid
RNA binding
RNA cleavage
RNA structure
sequence analysis
Anti-Bacterial Agents
Bacterial Proteins
Base Sequence
Cell Division
Cytoskeletal Proteins
Drug Design
Electrophoretic Mobility Shift Assay
Escherichia coli
Microscopy, Confocal
Molecular Sequence Data
Nucleic Acid Conformation
Oligoribonucleotides, Antisense
Promoter Regions, Genetic
Ribonuclease P
RNA Cleavage
Terminator Regions, Genetic
dc.description.none.fl_txt_mv EGS (external guide sequence) technology is a promising approach to designing new antibiotics. EGSs are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. The ftsZ mRNA secondary structure was modeled and EGSs complementary to two regions with high probability of being suitable targets were designed. In vitro reactions showed that EGSs targeting these regions bound ftsZ mRNA and elicited RNase P-mediated cleavage of ftsZ mRNA. A recombinant plasmid, pEGSb1, coding for an EGS that targets region "b" under the control of the T7 promoter was generated. Upon introduction of this plasmid into Escherichia coli BL21(DE3)(pLysS) the transformant strain formed filaments when expression of the EGS was induced. Concomitantly, E. coli harboring pEGSb1 showed a modest but significant inhibition of growth when synthesis of the EGSb1 was induced. Our results indicate that EGS technology could be a viable strategy to generate new antimicrobials targeting ftsZ. © 2012 Sala et al.
Fil:Soler-Bistué, A.J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Zorreguieta, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Tolmasky, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
description EGS (external guide sequence) technology is a promising approach to designing new antibiotics. EGSs are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. The ftsZ mRNA secondary structure was modeled and EGSs complementary to two regions with high probability of being suitable targets were designed. In vitro reactions showed that EGSs targeting these regions bound ftsZ mRNA and elicited RNase P-mediated cleavage of ftsZ mRNA. A recombinant plasmid, pEGSb1, coding for an EGS that targets region "b" under the control of the T7 promoter was generated. Upon introduction of this plasmid into Escherichia coli BL21(DE3)(pLysS) the transformant strain formed filaments when expression of the EGS was induced. Concomitantly, E. coli harboring pEGSb1 showed a modest but significant inhibition of growth when synthesis of the EGSb1 was induced. Our results indicate that EGS technology could be a viable strategy to generate new antimicrobials targeting ftsZ. © 2012 Sala et al.
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Sala
url http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Sala
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/2.5/ar
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/ar
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv PLoS ONE 2012;7(10)
reponame:Biblioteca Digital (UBA-FCEN)
instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
reponame_str Biblioteca Digital (UBA-FCEN)
collection Biblioteca Digital (UBA-FCEN)
instname_str Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron_str UBA-FCEN
institution UBA-FCEN
repository.name.fl_str_mv Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
repository.mail.fl_str_mv ana@bl.fcen.uba.ar
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score 12.623145

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