Induction of gliotoxin secretion in Aspergillus fumigatus by bacteria-associated molecules.
Aspergillus fumigatus is the most common causative agent of mold diseases in humans, giving rise to life-threatening infections in immunocompromised individuals. One of its secreted metabolites is gliotoxin, a toxic antimicrobial agent. The aim of this study was to determine whether the presence of pathogen-associated molecular patterns in broth cultures of A. fumigatus could induce gliotoxin production. Gliotoxin levels were analyzed by ultra-performance liquid chromatography and mass spectrometry. The presence of a bacteria-derived lipopolysaccharide, peptidoglycan, or lipoteichoic acid in the growth media at a concentration of 5 μg/ml increased the gliotoxin concentration in the media by 37%, 65%, and 35%, respectively. The findings reveal a correlation between the concentrations of pathogen-associated molecular patterns and gliotoxin secretion. This shows that there is a yet uncharacterized detection system for such compounds within fungi. Inducing secondary metabolite production by such means in fungi is potentially relevant for drug discovery research. Our results also give a possible explanation for the increased virulence of A. fumigatus during bacterial co-infection, one that is important for the transition from colonization to invasiveness in this pulmonary disease.
Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
K Stefan
KS
Svahn
Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
Ulf
U
Göransson
Department of Clinical Microbiology, Karolinska University Hospital & Karolinska Institute, Stockholm, Sweden.
Erja
E
Chryssanthou
Department of Medicinal Sciences, Uppsala University, Uppsala, Sweden.
Björn
B
Olsen
Department of Medicinal Sciences, Uppsala University, Uppsala, Sweden.
Jan
J
Sjölin
Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
Adam A
AA
Strömstedt
D001232:Aspergillus fumigatus / Q000378:metabolism* / Q000472:pathogenicity; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000737:chemistry; D005912:Gliotoxin / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000032:analysis / Q000494:pharmacology; D013058:Mass Spectrometry; D010457:Peptidoglycan / Q000032:analysis / Q000494:pharmacology; D013682:Teichoic Acids / Q000032:analysis / Q000494:pharmacology; D014774:Virulence
D003470:Culture Media; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D013682:Teichoic Acids; C009900:lipoteichoic acid; D005912:Gliotoxin