Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression

The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are...

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Main Authors: Peñuelas Urquides, Katia, Bermúdez de León, Mario, Silva Ramírez, Beatriz, Castorena Torres, Fabiola, Molina Salinas, Gloria María, Castro Garza, Jorge Enrique, Becerril Montes, Pola, Del Olmo, Esther, San Feliciano, Arturo, González Escalante, Laura Adiene, Villarreal Treviño, Licet, Said Fernández, Salvador
Format: Article
Language:English
Published: Frontiers Research Foundation 2021
Subjects:
Online Access:http://eprints.uanl.mx/23508/1/23508.pdf
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author Peñuelas Urquides, Katia
Bermúdez de León, Mario
Silva Ramírez, Beatriz
Castorena Torres, Fabiola
Molina Salinas, Gloria María
Castro Garza, Jorge Enrique
Becerril Montes, Pola
Del Olmo, Esther
San Feliciano, Arturo
González Escalante, Laura Adiene
Villarreal Treviño, Licet
Said Fernández, Salvador
author_facet Peñuelas Urquides, Katia
Bermúdez de León, Mario
Silva Ramírez, Beatriz
Castorena Torres, Fabiola
Molina Salinas, Gloria María
Castro Garza, Jorge Enrique
Becerril Montes, Pola
Del Olmo, Esther
San Feliciano, Arturo
González Escalante, Laura Adiene
Villarreal Treviño, Licet
Said Fernández, Salvador
author_sort Peñuelas Urquides, Katia
collection Repositorio Institucional
description The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are still unknown. The aim of this study was to evaluate the effect of UCI exposure on gene expression of drug-sensitive H37Rv and MDR CIBIN:UMF:15:99 clones of M. tuberculosis which were isolated, phenotypically, and genetically characterized, cultured to log phase and treated with UCI compounds; followed by total RNA isolation, reverse transcription and hybridization assays on Affymetrix genomic microarrays. Data were validated with RT-qPCR assays. As results, UCI-05 and UCI-14 exposure increased gltA1 expression in drug-sensitive H37Rv clones. Furthermore, UCI-05 increased lprQ expression in MDR CIBIN:UMF:15:99 M. tuberculosis clones while UCI-14 reduced the expression of this gene in drug-sensitive H37Rv clones. In addition, UCI-05 reduced rpsO expression in drug-sensitive H37Rv clones. We found gene expression alterations that suggest these molecules may alter carbon and lipid metabolism as well as interfere in the protein-producing machinery in M. tuberculosis.
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spelling eprints-235082022-06-30T20:35:36Z http://eprints.uanl.mx/23508/ Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression Peñuelas Urquides, Katia Bermúdez de León, Mario Silva Ramírez, Beatriz Castorena Torres, Fabiola Molina Salinas, Gloria María Castro Garza, Jorge Enrique Becerril Montes, Pola Del Olmo, Esther San Feliciano, Arturo González Escalante, Laura Adiene Villarreal Treviño, Licet Said Fernández, Salvador QR Microbiología The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are still unknown. The aim of this study was to evaluate the effect of UCI exposure on gene expression of drug-sensitive H37Rv and MDR CIBIN:UMF:15:99 clones of M. tuberculosis which were isolated, phenotypically, and genetically characterized, cultured to log phase and treated with UCI compounds; followed by total RNA isolation, reverse transcription and hybridization assays on Affymetrix genomic microarrays. Data were validated with RT-qPCR assays. As results, UCI-05 and UCI-14 exposure increased gltA1 expression in drug-sensitive H37Rv clones. Furthermore, UCI-05 increased lprQ expression in MDR CIBIN:UMF:15:99 M. tuberculosis clones while UCI-14 reduced the expression of this gene in drug-sensitive H37Rv clones. In addition, UCI-05 reduced rpsO expression in drug-sensitive H37Rv clones. We found gene expression alterations that suggest these molecules may alter carbon and lipid metabolism as well as interfere in the protein-producing machinery in M. tuberculosis. Frontiers Research Foundation 2021 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/23508/1/23508.pdf http://eprints.uanl.mx/23508/1.haspreviewThumbnailVersion/23508.pdf Peñuelas Urquides, Katia y Bermúdez de León, Mario y Silva Ramírez, Beatriz y Castorena Torres, Fabiola y Molina Salinas, Gloria María y Castro Garza, Jorge Enrique y Becerril Montes, Pola y Del Olmo, Esther y San Feliciano, Arturo y González Escalante, Laura Adiene y Villarreal Treviño, Licet y Said Fernández, Salvador (2021) Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression. Frontiers in Microbiology, 12. pp. 1-11. ISSN 1664-302X http://doi.org/10.3389/fmicb.2021.742867 doi:10.3389/fmicb.2021.742867
spellingShingle QR Microbiología
Peñuelas Urquides, Katia
Bermúdez de León, Mario
Silva Ramírez, Beatriz
Castorena Torres, Fabiola
Molina Salinas, Gloria María
Castro Garza, Jorge Enrique
Becerril Montes, Pola
Del Olmo, Esther
San Feliciano, Arturo
González Escalante, Laura Adiene
Villarreal Treviño, Licet
Said Fernández, Salvador
Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression
title_full Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression
title_fullStr Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression
title_full_unstemmed Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression
title_short Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression
title_sort two new dihydrosphingosine analogs against mycobacterium tuberculosis affect glta1 lprq and rpso expression
topic QR Microbiología
url http://eprints.uanl.mx/23508/1/23508.pdf
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