Sit and wait: Special features of Aspergillus terreus in macrophage interactions and virulence

M. Brock, I.D. Jacobsen

Author address: 

Microbial Biochemistry/Physiology, Friedrich Schiller University and Hans Knoell Institute, Jena, Germany

Abstract: 

While Aspergillus fumigatus is known as the main cause of invasive pulmonary aspergillosis in immunocompromised patients, Aspergillus terreus is an emerging pathogen prevalent in some local hot spots. When tested in embryonated egg or murine infection models A. terreus required substantially higher infectious doses compared to A. fumigatus to cause high mortality rates. Furthermore, when A. fumigatus and A. terreus infections were followed by in vivo imaging using bioluminescent reporter strains, germination and tissue invasion of A. terreus was significantly delayed. To elucidate differences in more detail, the interaction of A. terreus and A. fumigatus with macrophages was compared. A. terreus was phagocytosed significantly faster, which appears mainly due to higher exposure of galactomannan and glucans on the surface of conidia. Additionally, although phagocytosis of both species resulted in phagolysosome maturation, A. fumigatus efficiently inhibited acidification, which was not the case for A. terreus. However, within this acidic environment of phagolysosomes A. terreus showed long-term persistence without significant inactivation of conidia. Further analyses revealed that inefficient blocking of acidification by A. terreus was due to differences in the spore colour pigment of both species. Recombinant production of a naphthopyrone synthase from Aspergillus nidulans enabled A. terreus to inhibit the acidification to a similar extent as observed for A. fumigatus. This alteration of the phagolysosomal environment resulted in an increased escape from macrophages and was accompanied by increased virulence in a murine infection model. We speculate that the long-term persistence of A. terreus wild-type strains in acidified phagolysosomes might be responsible for high dissemination rates observed in infected human patients, because A. terreusmight hitchhike inside immune effector cells to reach secondary sites of infection
2013

abstract No: 

N/A

Full conference title: 

27th Fungal Genetics Conference
    • Fungal Genetics Conference 27th (2013)