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New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis

In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through...

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Autores principales: Parada, Cristina, Neri-Badillo, Isabel Cecilia, Vallecillo, Antonio J., Segura, Erika, Silva-Miranda, Mayra, Guzmán-Gutiérrez, Silvia Laura, Ortega, Paola A., Coronado-Aceves, Enrique Wenceslao, Cancino-Villeda, Laura, Torres-Larios, Alfredo, Aceves Sánchez, Michel de Jesús, Flores Valdez, Mario Alberto, Espitia, Clara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467707/
https://www.ncbi.nlm.nih.gov/pubmed/34578171
http://dx.doi.org/10.3390/pathogens10091139
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author Parada, Cristina
Neri-Badillo, Isabel Cecilia
Vallecillo, Antonio J.
Segura, Erika
Silva-Miranda, Mayra
Guzmán-Gutiérrez, Silvia Laura
Ortega, Paola A.
Coronado-Aceves, Enrique Wenceslao
Cancino-Villeda, Laura
Torres-Larios, Alfredo
Aceves Sánchez, Michel de Jesús
Flores Valdez, Mario Alberto
Espitia, Clara
author_facet Parada, Cristina
Neri-Badillo, Isabel Cecilia
Vallecillo, Antonio J.
Segura, Erika
Silva-Miranda, Mayra
Guzmán-Gutiérrez, Silvia Laura
Ortega, Paola A.
Coronado-Aceves, Enrique Wenceslao
Cancino-Villeda, Laura
Torres-Larios, Alfredo
Aceves Sánchez, Michel de Jesús
Flores Valdez, Mario Alberto
Espitia, Clara
author_sort Parada, Cristina
collection PubMed
description In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through its C-terminal lysine-rich domain, this surface antigen interacts with heparan sulfate proteoglycans present in non-phagocytic cells, leading to extrapulmonary dissemination of the pathogen. In this study, the adhesin was expressed as a recombinant methylated protein in Rhodococcus erythropolis L88 and it was found associated to lipid droplets when bacteria were grown under nitrogen limitation. In order to delve into the role methylation could have in host–pathogen interactions, a comparative analysis was carried out between methylated and unmethylated protein produced in Escherichia coli. We found that methylation had an impact on lowering protein isoelectric point, but no differences between the proteins were found in their capacity to interact with heparin and A549 epithelial cells. An important finding was that HbhA is a Fatty Acid Binding Protein and differences in the conformational stability of the protein in complex with the fatty acid were observed between methylated and unmethylated protein. Together, these results suggest that the described role for this mycobacteria protein in lipid bodies formation could be related to its capacity to transport fatty acids. Obtained results also provide new clues about the role HbhA methylation could have in tuberculosis and point out the importance of having heterologous expression systems to obtain modified proteins.
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spelling pubmed-84677072021-09-27 New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis Parada, Cristina Neri-Badillo, Isabel Cecilia Vallecillo, Antonio J. Segura, Erika Silva-Miranda, Mayra Guzmán-Gutiérrez, Silvia Laura Ortega, Paola A. Coronado-Aceves, Enrique Wenceslao Cancino-Villeda, Laura Torres-Larios, Alfredo Aceves Sánchez, Michel de Jesús Flores Valdez, Mario Alberto Espitia, Clara Pathogens Article In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through its C-terminal lysine-rich domain, this surface antigen interacts with heparan sulfate proteoglycans present in non-phagocytic cells, leading to extrapulmonary dissemination of the pathogen. In this study, the adhesin was expressed as a recombinant methylated protein in Rhodococcus erythropolis L88 and it was found associated to lipid droplets when bacteria were grown under nitrogen limitation. In order to delve into the role methylation could have in host–pathogen interactions, a comparative analysis was carried out between methylated and unmethylated protein produced in Escherichia coli. We found that methylation had an impact on lowering protein isoelectric point, but no differences between the proteins were found in their capacity to interact with heparin and A549 epithelial cells. An important finding was that HbhA is a Fatty Acid Binding Protein and differences in the conformational stability of the protein in complex with the fatty acid were observed between methylated and unmethylated protein. Together, these results suggest that the described role for this mycobacteria protein in lipid bodies formation could be related to its capacity to transport fatty acids. Obtained results also provide new clues about the role HbhA methylation could have in tuberculosis and point out the importance of having heterologous expression systems to obtain modified proteins. MDPI 2021-09-04 /pmc/articles/PMC8467707/ /pubmed/34578171 http://dx.doi.org/10.3390/pathogens10091139 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parada, Cristina
Neri-Badillo, Isabel Cecilia
Vallecillo, Antonio J.
Segura, Erika
Silva-Miranda, Mayra
Guzmán-Gutiérrez, Silvia Laura
Ortega, Paola A.
Coronado-Aceves, Enrique Wenceslao
Cancino-Villeda, Laura
Torres-Larios, Alfredo
Aceves Sánchez, Michel de Jesús
Flores Valdez, Mario Alberto
Espitia, Clara
New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis
title New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis
title_full New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis
title_fullStr New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis
title_full_unstemmed New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis
title_short New Insights into the Methylation of Mycobacterium tuberculosis Heparin Binding Hemagglutinin Adhesin Expressed in Rhodococcus erythropolis
title_sort new insights into the methylation of mycobacterium tuberculosis heparin binding hemagglutinin adhesin expressed in rhodococcus erythropolis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467707/
https://www.ncbi.nlm.nih.gov/pubmed/34578171
http://dx.doi.org/10.3390/pathogens10091139
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