Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.

Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable syst...

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Autores principales:	Ashok K Chaturvedi, Anna L Lazzell, Stephen P Saville, Floyd L Wormley, Carlos Monteagudo, Jose L Lopez-Ribot
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3bb94cde87fd46d4988ff9c45b72af73
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spelling	oai:doaj.org-article:3bb94cde87fd46d4988ff9c45b72af732021-11-18T06:53:18ZValidation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.1932-620310.1371/journal.pone.0020449https://doaj.org/article/3bb94cde87fd46d4988ff9c45b72af732011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21633704/?tool=EBIhttps://doaj.org/toc/1932-6203Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases.Ashok K ChaturvediAnna L LazzellStephen P SavilleFloyd L WormleyCarlos MonteagudoJose L Lopez-RibotPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20449 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ashok K Chaturvedi Anna L Lazzell Stephen P Saville Floyd L Wormley Carlos Monteagudo Jose L Lopez-Ribot Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
description	Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases.
format	article
author	Ashok K Chaturvedi Anna L Lazzell Stephen P Saville Floyd L Wormley Carlos Monteagudo Jose L Lopez-Ribot
author_facet	Ashok K Chaturvedi Anna L Lazzell Stephen P Saville Floyd L Wormley Carlos Monteagudo Jose L Lopez-Ribot
author_sort	Ashok K Chaturvedi
title	Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
title_short	Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
title_full	Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
title_fullStr	Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
title_full_unstemmed	Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
title_sort	validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3bb94cde87fd46d4988ff9c45b72af73
work_keys_str_mv	AT ashokkchaturvedi validationofthetetracyclineregulatablegeneexpressionsystemforthestudyofthepathogenesisofinfectiousdisease AT annallazzell validationofthetetracyclineregulatablegeneexpressionsystemforthestudyofthepathogenesisofinfectiousdisease AT stephenpsaville validationofthetetracyclineregulatablegeneexpressionsystemforthestudyofthepathogenesisofinfectiousdisease AT floydlwormley validationofthetetracyclineregulatablegeneexpressionsystemforthestudyofthepathogenesisofinfectiousdisease AT carlosmonteagudo validationofthetetracyclineregulatablegeneexpressionsystemforthestudyofthepathogenesisofinfectiousdisease AT josellopezribot validationofthetetracyclineregulatablegeneexpressionsystemforthestudyofthepathogenesisofinfectiousdisease
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Validation of the tetracycline regulatable gene expression system for the study of the pathogenesis of infectious disease.

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