Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus 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. Nevertheless, studies regarding bmGT production among common opportunistic fungi, including the 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 genus we have assessed bmGT production within the genus , including , , , and , and its correlation with presence. In order to validate the relevance of our findings, we compared bmGT during culture with the presence of bmGT in sera of patients from whom the spp. were isolated. Our results indicate that most isolates produce GT and bmGT both and . In contrast, and were not able to produce GT or bmGT, although produced bmGT from a exogenous GT source. The frequency and amount of bmGT production in and isolates was lower than in . Our results suggest that this defect could be related to the culture conditions, since isolates that did not produce bmGT were able to synthetize it . In summary, our study indicates that bmGT could be very useful to specifically detect the presence of , the most prevalent agent causing IA. Concerning and a higher number of analyses from sera from infected patients will be required to reach a useful conclusion.