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...
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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 |