Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions
Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), is one of the ten leading causes of death worldwide affecting mainly developing countries. Mtb can persist and survive inside infected cells through modulation of host antibacterial attack, i.e., by avoiding the maturation of p...
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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Frontiers Media
2021
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2020.570794/full http://hdl.handle.net/20.500.12123/8668 https://doi.org/10.3389/fmicb.2020.570794 |
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| author | Forrellad, Marina Andrea Blanco, Federico Carlos Marrero Diaz De Vill, Rubén Vazquez, Cristina Lourdes Yaneff, Agustín Garcia, Elizabeth Andrea Gutierrez, Maximiliano Gabriel Durán, Rosario Villarino, Andrea Bigi, Fabiana |
| author_browse | Bigi, Fabiana Blanco, Federico Carlos Durán, Rosario Forrellad, Marina Andrea Garcia, Elizabeth Andrea Gutierrez, Maximiliano Gabriel Marrero Diaz De Vill, Rubén Vazquez, Cristina Lourdes Villarino, Andrea Yaneff, Agustín |
| author_facet | Forrellad, Marina Andrea Blanco, Federico Carlos Marrero Diaz De Vill, Rubén Vazquez, Cristina Lourdes Yaneff, Agustín Garcia, Elizabeth Andrea Gutierrez, Maximiliano Gabriel Durán, Rosario Villarino, Andrea Bigi, Fabiana |
| author_sort | Forrellad, Marina Andrea |
| collection | INTA Digital |
| description | Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), is one of the ten leading causes of death worldwide affecting mainly developing countries. Mtb can persist and survive inside infected cells through modulation of host antibacterial attack, i.e., by avoiding the maturation of phagosome containing mycobacteria to more acidic endosomal compartment. In addition, bacterial phosphatases play a central role in the interplay between host cells and Mtb. In this study, we characterized the Rv2577 of Mtb as a potential alkaline phosphatase/phosphodiesterase enzyme. By an in vitro kinetic assay, we demonstrated that purified Rv2577 expressed in Mycobacterium smegmatis displays both enzyme activities, as evidenced by using the artificial substrates p-NPP and bis-(p-NPP). In addition, a three-dimensional model of Rv2577 allowed us to define the catalytic amino acid residues of the active site, which were confirmed by site-directed mutagenesis and enzyme activity analysis, being characteristic of a member of the metallophosphatase superfamily. Finally, a mutation introduced in Rv2577 reduced the replication of Mtb in mouse organs and impaired the arrest of phagosomes containing mycobacteria in early endosomes; which indicates Rv2577 plays a role in Mtb virulence. |
| format | info:ar-repo/semantics/artículo |
| id | INTA8668 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| record_format | dspace |
| spelling | INTA86682021-02-17T14:49:57Z Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions Forrellad, Marina Andrea Blanco, Federico Carlos Marrero Diaz De Vill, Rubén Vazquez, Cristina Lourdes Yaneff, Agustín Garcia, Elizabeth Andrea Gutierrez, Maximiliano Gabriel Durán, Rosario Villarino, Andrea Bigi, Fabiana Mycobacterium tuberculosis Virulencia Tuberculosis Virulence Phosphodiesterase Phosphatase Fosfatasa Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), is one of the ten leading causes of death worldwide affecting mainly developing countries. Mtb can persist and survive inside infected cells through modulation of host antibacterial attack, i.e., by avoiding the maturation of phagosome containing mycobacteria to more acidic endosomal compartment. In addition, bacterial phosphatases play a central role in the interplay between host cells and Mtb. In this study, we characterized the Rv2577 of Mtb as a potential alkaline phosphatase/phosphodiesterase enzyme. By an in vitro kinetic assay, we demonstrated that purified Rv2577 expressed in Mycobacterium smegmatis displays both enzyme activities, as evidenced by using the artificial substrates p-NPP and bis-(p-NPP). In addition, a three-dimensional model of Rv2577 allowed us to define the catalytic amino acid residues of the active site, which were confirmed by site-directed mutagenesis and enzyme activity analysis, being characteristic of a member of the metallophosphatase superfamily. Finally, a mutation introduced in Rv2577 reduced the replication of Mtb in mouse organs and impaired the arrest of phagosomes containing mycobacteria in early endosomes; which indicates Rv2577 plays a role in Mtb virulence. Instituto de Biotecnología Fil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marrero Diaz de Villegas, Rubén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Yaneff, Agustín. Universidad de Buenos Aires. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gutierrez, Maximiliano Gabriel. The Francis Crick Institute, Host-Pathogen Interactions in Tuberculosis Laboratory; Reino Unido Fil: Durán, Rosario. Institut Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biológicas Clemente Estable; Uruguay Fil: Villarino, Andrea. Universidad de la República (UdelaR). Facultad de Ciencias. Sección Bioquímica; Uruguay Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentina 2021-02-17T14:45:16Z 2021-02-17T14:45:16Z 2020-10 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.frontiersin.org/articles/10.3389/fmicb.2020.570794/full http://hdl.handle.net/20.500.12123/8668 1664-302X https://doi.org/10.3389/fmicb.2020.570794 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Frontiers Media Frontiers in Microbiology 11 : 570794 (Octubre 2020) |
| spellingShingle | Mycobacterium tuberculosis Virulencia Tuberculosis Virulence Phosphodiesterase Phosphatase Fosfatasa Forrellad, Marina Andrea Blanco, Federico Carlos Marrero Diaz De Vill, Rubén Vazquez, Cristina Lourdes Yaneff, Agustín Garcia, Elizabeth Andrea Gutierrez, Maximiliano Gabriel Durán, Rosario Villarino, Andrea Bigi, Fabiana Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| title | Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| title_full | Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| title_fullStr | Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| title_full_unstemmed | Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| title_short | Rv2577 of Mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| title_sort | rv2577 of mycobacterium tuberculosis is a virulence factor with dual phosphatase and phosphodiesterase functions |
| topic | Mycobacterium tuberculosis Virulencia Tuberculosis Virulence Phosphodiesterase Phosphatase Fosfatasa |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2020.570794/full http://hdl.handle.net/20.500.12123/8668 https://doi.org/10.3389/fmicb.2020.570794 |
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