Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis

Targeted gene disruption by homologous recombination, has been widely used in mycobacterium species to understand the genetic basis of virulence and persistence in the host and to develop efficacious potential live vaccines. However, in slow growing pathogenic mycobacteria as Mycobacterium avium sub...

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Main Authors: Alonso, Maria Natalia, Malaga, Wladimir, Mc Neil, Michael, Jackson, Mary, Romano, Maria Isabel, Guilhot, Christophe, Santangelo, María De La Paz
Format: info:ar-repo/semantics/artículo
Language:Inglés
Published: Elsevier 2020
Subjects:
Online Access:http://hdl.handle.net/20.500.12123/7753
https://www.sciencedirect.com/science/article/pii/S0923250820300383
https://doi.org/10.1016/j.resmic.2020.04.001
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author Alonso, Maria Natalia
Malaga, Wladimir
Mc Neil, Michael
Jackson, Mary
Romano, Maria Isabel
Guilhot, Christophe
Santangelo, María De La Paz
author_browse Alonso, Maria Natalia
Guilhot, Christophe
Jackson, Mary
Malaga, Wladimir
Mc Neil, Michael
Romano, Maria Isabel
Santangelo, María De La Paz
author_facet Alonso, Maria Natalia
Malaga, Wladimir
Mc Neil, Michael
Jackson, Mary
Romano, Maria Isabel
Guilhot, Christophe
Santangelo, María De La Paz
author_sort Alonso, Maria Natalia
collection INTA Digital
description Targeted gene disruption by homologous recombination, has been widely used in mycobacterium species to understand the genetic basis of virulence and persistence in the host and to develop efficacious potential live vaccines. However, in slow growing pathogenic mycobacteria as Mycobacterium avium subsp paratuberculosis (MAP), these methods have been inefficient, in part due to the low frequency of legitimate homologous recombination. Another feature of mycobacteria is the low efficiency of transformation; therefore, some years ago, a phage-mediated transduction process was developed to introduce DNA into mycobacteria. This strategy is very efficient, due to the high rate of infection of the phage. This report describes a genetic method for the generation of targeted deletion mutations in MAP by allelic exchange using in vitro-generated specialized transducing mycobacteriophages, which does not require the critical packaging step and that could also be applied to other mycobacteria. We provide a detailed gene deletion methodology and demonstrate the use of this genetic system by deleting the mce4 operon of MAP. Finally, our results showed that the deletion of mce4 in MAP induces triacylglycerol accumulation; alter morphology and aggregation in liquid culture.
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institution Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina)
language Inglés
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publishDateRange 2020
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spelling INTA77532020-08-21T12:49:57Z Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis Alonso, Maria Natalia Malaga, Wladimir Mc Neil, Michael Jackson, Mary Romano, Maria Isabel Guilhot, Christophe Santangelo, María De La Paz Mycobacterium Mycobacterium avium subsp. paratuberculosis Triglicéridos Mutación Genética Triglycerides Mutation Genetics Targeted gene disruption by homologous recombination, has been widely used in mycobacterium species to understand the genetic basis of virulence and persistence in the host and to develop efficacious potential live vaccines. However, in slow growing pathogenic mycobacteria as Mycobacterium avium subsp paratuberculosis (MAP), these methods have been inefficient, in part due to the low frequency of legitimate homologous recombination. Another feature of mycobacteria is the low efficiency of transformation; therefore, some years ago, a phage-mediated transduction process was developed to introduce DNA into mycobacteria. This strategy is very efficient, due to the high rate of infection of the phage. This report describes a genetic method for the generation of targeted deletion mutations in MAP by allelic exchange using in vitro-generated specialized transducing mycobacteriophages, which does not require the critical packaging step and that could also be applied to other mycobacteria. We provide a detailed gene deletion methodology and demonstrate the use of this genetic system by deleting the mce4 operon of MAP. Finally, our results showed that the deletion of mce4 in MAP induces triacylglycerol accumulation; alter morphology and aggregation in liquid culture. Instituto de Biotecnología Fil: Alonso, Maria Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Malaga, Wladimir. University of Toulouse. Institut de Pharmacologie et de Biologie Structurale; Francia Fil: Mc Neil, Michael. Colorado State University. Department of Microbiology, Immunology and Pathology. Mycobacteria Research Laboratories; Estados Unidos Fil: Jackson, Mary. Colorado State University. Department of Microbiology, Immunology and Pathology. Mycobacteria Research Laboratories; Estados Unidos Fil: Romano, Maria Isabel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guilhot, Christophe. University of Toulouse. Institut de Pharmacologie et de Biologie Structurale; Francia Fil: Santangelo, María De La Paz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2020-08-21T12:45:54Z 2020-08-21T12:45:54Z 2020-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/7753 https://www.sciencedirect.com/science/article/pii/S0923250820300383 0923-2508 https://doi.org/10.1016/j.resmic.2020.04.001 eng info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Research in Microbiology 171 (5–6) : 203-210 (July–September 2020)
spellingShingle Mycobacterium
Mycobacterium avium subsp. paratuberculosis
Triglicéridos
Mutación
Genética
Triglycerides
Mutation
Genetics
Alonso, Maria Natalia
Malaga, Wladimir
Mc Neil, Michael
Jackson, Mary
Romano, Maria Isabel
Guilhot, Christophe
Santangelo, María De La Paz
Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis
title Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis
title_full Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis
title_fullStr Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis
title_full_unstemmed Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis
title_short Efficient method for targeted gene disruption by homologous recombination in Mycobacterium avium subspecie paratuberculosis
title_sort efficient method for targeted gene disruption by homologous recombination in mycobacterium avium subspecie paratuberculosis
topic Mycobacterium
Mycobacterium avium subsp. paratuberculosis
Triglicéridos
Mutación
Genética
Triglycerides
Mutation
Genetics
url http://hdl.handle.net/20.500.12123/7753
https://www.sciencedirect.com/science/article/pii/S0923250820300383
https://doi.org/10.1016/j.resmic.2020.04.001
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