title: Bis(methyl)gliotoxin proves to be a more stable and reliable marker for invasive aspergillosis than gliotoxin and suitable for use in diagnosis.
abstract: The virulence factor gliotoxin (GT) and its inactive derivative, bis(methylthio)gliotoxin (bmGT), are produced by pathogens of the genus Aspergillus. Here we report the detection of GT and bmGT in serum of humans at risk of invasive aspergillosis (IA) as well as in cultures of fungal isolates derived from patients with proven infection with A. fumigatus. Although both compounds are readily recoverable from spiked human serum or plasma, only bmGT is retained in whole blood, indicating that bmGT may be the better marker for in vivo detection. Accordingly, bmGT was found more frequently than GT in samples from patients at risk of IA and incultures of clinical isolates of A. fumigatus. In some cases, bmGT was detected before mycologic evidence ofinfection was gained. Importantly, neither GT nor bmGT was found in serum from healthy donors or from neutropenic patients without any sign of infection. Thus, bmGT presence might provide a more reliable indicator of A. fumigatus infections than GT. Due to its simplicity and sensitivity, a diagnostic technology based on this test could be easily adopted in clinical laboratories to help in the diagnosis of this often fatal fungal infection.
authors.affiliation: Instituto de Carboquímica ICB-CSIC, Zaragoza, Spain.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Domingo
authors.forename: Cristina
authors.initials: C
authors.lastname: Colmenarejo
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Lostao
authors.forename: Arno
authors.initials: A
authors.lastname: Müllbacher
authors.forename: Carmen
authors.initials: C
authors.lastname: Jarne
authors.forename: María J
authors.initials: MJ
authors.lastname: Revillo
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Lourdes
authors.initials: L
authors.lastname: Roc
authors.forename: Jacques F
authors.initials: JF
authors.lastname: Meis
authors.forename: Antonio
authors.initials: A
authors.lastname: Rezusta
authors.forename: Julian
authors.initials: J
authors.lastname: Pardo
authors.forename: Eva M
authors.initials: EM
authors.lastname: Gálvez
mesh_terms: D001228:Aspergillosis / Q000175:diagnosis*; D001232:Aspergillus fumigatus / Q000302:isolation & purification* / Q000378:metabolism; D001774:Blood Chemical Analysis; D003470:Culture Media / Q000737:chemistry; D005912:Gliotoxin / Q000031:analogs & derivatives* / Q000097:blood*; D006801:Humans; D012680:Sensitivity and Specificity; D037521:Virulence Factors / Q000097:blood
chemical_list: D003470:Culture Media; D037521:Virulence Factors; D005912:Gliotoxin; C048665:bisdethiobis(methylthio)gliotoxin