Gliotoxin, a Known Virulence Factor in the Major Human Pathogen Aspergillus fumigatus, Is Also Biosynthesized by Its Nonpathogenic Relative <i>Aspergillus fischeri</i>
Sonja L. Knowles, Matthew E. Mead, Lilian Pereira Silva, Huzefa A. Raja, Jacob L. Steenwyk, Gustavo H. Goldman, Nicholas H. Oberlies, Antonis Rokas
Abstract
Aspergillus fumigatus is a major opportunistic fungal pathogen of humans, but most of its close relatives are nonpathogenic. Why is that so? This important, yet largely unanswered, question can be addressed by examining how A. fumigatus and its close nonpathogenic relatives are similar or different with respect to virulence-associated traits. We investigated whether Aspergillus fischeri , a nonpathogenic close relative of A. fumigatus , can produce gliotoxin, a mycotoxin known to contribute to A. fumigatus virulence. We discovered that the nonpathogenic A. fischeri produces gliotoxin under the same conditions as those of the major pathogen A. fumigatus . However, we also discovered that, in contrast to what has previously been observed in A. fumigatus , the loss of secondary metabolite production in A. fischeri does not alter its virulence. Our results are consistent with the “cards of virulence” model of opportunistic fungal disease, in which the ability to cause disease stems from the combination (“hand”) of virulence factors (“cards”) but not from individual factors per se .