Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis
Gliotoxin (GT) is a fungal secondary metabolite that has attracted great interest due to its high biological activity since it was discovered by the 1930s. An inactive derivative of this molecule, bis(methylthio)gliotoxin (bmGT), has been proposed as an invasive aspergillosis (IA) biomarker. Neverth...
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doaj-1f82b2fb9a04400790a04f01ac87d7322020-11-24T22:39:29ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-06-01910.3389/fmicb.2018.01246369217Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic AnalysisMatxalen Vidal-García0Matxalen Vidal-García1Sergio Redrado2M. Pilar Domingo3Patricia Marquina4Cristina Colmenarejo5Jacques F. Meis6Jacques F. Meis7Antonio Rezusta8Antonio Rezusta9Julian Pardo10Julian Pardo11Julian Pardo12Julian Pardo13Eva M. Galvez14Centro de Investigación Biomédica de Aragón, Instituto de Investigación Sanitaria Aragón, Zaragoza, SpainHospital Universitario Miguel Servet, Zaragoza, SpainInstituto de Carboquímica, Zaragoza, SpainInstituto de Carboquímica, Zaragoza, SpainInstituto de Carboquímica, Zaragoza, SpainHospital Universitario Miguel Servet, Zaragoza, SpainDepartment of Medical Microbiology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, NetherlandsHospital Universitario Miguel Servet, Zaragoza, SpainDepartamento de Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, Zaragoza, SpainCentro de Investigación Biomédica de Aragón, Instituto de Investigación Sanitaria Aragón, Zaragoza, SpainFundacion Agencia Aragonesa para la Investigacion y el Desarrollo, Zaragoza, SpainDepartamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, SpainInstituto de Nanociencia de Aragón, Zaragoza, SpainInstituto de Carboquímica, Zaragoza, SpainGliotoxin (GT) is a fungal secondary metabolite that has attracted great interest due to its high biological activity since it was discovered by the 1930s. An inactive derivative of this molecule, bis(methylthio)gliotoxin (bmGT), has been proposed as an invasive aspergillosis (IA) biomarker. Nevertheless, studies regarding bmGT production among common opportunistic fungi, including the Aspergillus genus, are scarce and sometimes discordant. As previously reported, bmGT is produced from GT by a methyl-transferase, named as GtmA, as a negative feedback regulatory system of GT production. In order to analyze the potential of bmGT detection to enable identification of infections caused by different members of the Aspergillus genus we have assessed bmGT production within the genus Aspergillus, including A, fumigatus, A. niger, A. nidulans, and A. flavus, and its correlation with gtmA presence. In order to validate the relevance of our in vitro findings, we compared bmGT during in vitro culture with the presence of bmGT in sera of patients from whom the Aspergillus spp. were isolated. Our results indicate that most A. fumigatus isolates produce GT and bmGT both in vitro and in vivo. In contrast, A. niger and A. nidulans were not able to produce GT or bmGT, although A. niger produced bmGT from a exogenous GT source. The frequency and amount of bmGT production in A. terreus and A. flavus isolates in vitro was lower than in A. fumigatus. Our results suggest that this defect could be related to the in vitro culture conditions, since isolates that did not produce bmGT in vitro were able to synthetize it in vivo. In summary, our study indicates that bmGT could be very useful to specifically detect the presence of A. fumigatus, the most prevalent agent causing IA. Concerning A. terreus and A. flavus a higher number of analyses from sera from infected patients will be required to reach a useful conclusion.https://www.frontiersin.org/article/10.3389/fmicb.2018.01246/fullbis(methylthio)gliotoxinAspergillus spp.gtmAinvasive aspergillosisbiomarker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matxalen Vidal-García Matxalen Vidal-García Sergio Redrado M. Pilar Domingo Patricia Marquina Cristina Colmenarejo Jacques F. Meis Jacques F. Meis Antonio Rezusta Antonio Rezusta Julian Pardo Julian Pardo Julian Pardo Julian Pardo Eva M. Galvez |
spellingShingle |
Matxalen Vidal-García Matxalen Vidal-García Sergio Redrado M. Pilar Domingo Patricia Marquina Cristina Colmenarejo Jacques F. Meis Jacques F. Meis Antonio Rezusta Antonio Rezusta Julian Pardo Julian Pardo Julian Pardo Julian Pardo Eva M. Galvez Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis Frontiers in Microbiology bis(methylthio)gliotoxin Aspergillus spp. gtmA invasive aspergillosis biomarker |
author_facet |
Matxalen Vidal-García Matxalen Vidal-García Sergio Redrado M. Pilar Domingo Patricia Marquina Cristina Colmenarejo Jacques F. Meis Jacques F. Meis Antonio Rezusta Antonio Rezusta Julian Pardo Julian Pardo Julian Pardo Julian Pardo Eva M. Galvez |
author_sort |
Matxalen Vidal-García |
title |
Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis |
title_short |
Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis |
title_full |
Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis |
title_fullStr |
Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis |
title_full_unstemmed |
Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis |
title_sort |
production of the invasive aspergillosis biomarker bis(methylthio)gliotoxin within the genus aspergillus: in vitro and in vivo metabolite quantification and genomic analysis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2018-06-01 |
description |
Gliotoxin (GT) is a fungal secondary metabolite that has attracted great interest due to its high biological activity since it was discovered by the 1930s. An inactive derivative of this molecule, bis(methylthio)gliotoxin (bmGT), has been proposed as an invasive aspergillosis (IA) biomarker. Nevertheless, studies regarding bmGT production among common opportunistic fungi, including the Aspergillus genus, are scarce and sometimes discordant. As previously reported, bmGT is produced from GT by a methyl-transferase, named as GtmA, as a negative feedback regulatory system of GT production. In order to analyze the potential of bmGT detection to enable identification of infections caused by different members of the Aspergillus genus we have assessed bmGT production within the genus Aspergillus, including A, fumigatus, A. niger, A. nidulans, and A. flavus, and its correlation with gtmA presence. In order to validate the relevance of our in vitro findings, we compared bmGT during in vitro culture with the presence of bmGT in sera of patients from whom the Aspergillus spp. were isolated. Our results indicate that most A. fumigatus isolates produce GT and bmGT both in vitro and in vivo. In contrast, A. niger and A. nidulans were not able to produce GT or bmGT, although A. niger produced bmGT from a exogenous GT source. The frequency and amount of bmGT production in A. terreus and A. flavus isolates in vitro was lower than in A. fumigatus. Our results suggest that this defect could be related to the in vitro culture conditions, since isolates that did not produce bmGT in vitro were able to synthetize it in vivo. In summary, our study indicates that bmGT could be very useful to specifically detect the presence of A. fumigatus, the most prevalent agent causing IA. Concerning A. terreus and A. flavus a higher number of analyses from sera from infected patients will be required to reach a useful conclusion. |
topic |
bis(methylthio)gliotoxin Aspergillus spp. gtmA invasive aspergillosis biomarker |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2018.01246/full |
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