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

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 compleme...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Sala, C.D., Soler-Bistué, A.J.C., Korprapun, L., Zorreguieta, A., Tolmasky, M.E.
Formato: Artículo publishedVersion
Publicado: 2012
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Sala
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_19326203_v7_n10_p_Sala_oai
Aporte de:
id I28-R145-paper_19326203_v7_n10_p_Sala_oai
record_format dspace
spelling I28-R145-paper_19326203_v7_n10_p_Sala_oai2024-08-16 Sala, C.D. Soler-Bistué, A.J.C. Korprapun, L. Zorreguieta, A. Tolmasky, M.E. 2012 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. application/pdf http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Sala info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar PLoS ONE 2012;7(10) 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 Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_19326203_v7_n10_p_Sala_oai
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
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
spellingShingle 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
Sala, C.D.
Soler-Bistué, A.J.C.
Korprapun, L.
Zorreguieta, A.
Tolmasky, M.E.
Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
topic_facet 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
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.
format Artículo
Artículo
publishedVersion
author Sala, C.D.
Soler-Bistué, A.J.C.
Korprapun, L.
Zorreguieta, A.
Tolmasky, M.E.
author_facet Sala, C.D.
Soler-Bistué, A.J.C.
Korprapun, L.
Zorreguieta, A.
Tolmasky, M.E.
author_sort Sala, C.D.
title Inhibition of Cell Division Induced by External Guide Sequences (EGS Technology) Targeting ftsZ
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
publishDate 2012
url http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Sala
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_19326203_v7_n10_p_Sala_oai
work_keys_str_mv AT salacd inhibitionofcelldivisioninducedbyexternalguidesequencesegstechnologytargetingftsz
AT solerbistueajc inhibitionofcelldivisioninducedbyexternalguidesequencesegstechnologytargetingftsz
AT korprapunl inhibitionofcelldivisioninducedbyexternalguidesequencesegstechnologytargetingftsz
AT zorreguietaa inhibitionofcelldivisioninducedbyexternalguidesequencesegstechnologytargetingftsz
AT tolmaskyme inhibitionofcelldivisioninducedbyexternalguidesequencesegstechnologytargetingftsz
_version_ 1809357034051600384