Program Book - 27th Fungal Genetics Conference

CONCURRENT SESSION ABSTRACTSNematode-trapping fungi eavesdrop on nematode pheromones. Yen-Ping Hsueh 1 , Parag Mahanti 2 , Frank Schroeder 2 , Paul Sternberg 1 . 1) Howard HughesMedical Institute and Division of Biology, California Inst of Technology, Pasadena, CA; 2) Boyce Thompson Institute and Department of Chemistry andChemical Biology, Cornell University, Ithaca, NY.The recognition of molecular patterns associated with specific pathogens or food sources is fundamental to ecology and plays a major role in theevolution of predator-prey relationships. Recent studies showed that nematodes produce an evolutionarily highly conserved family of small molecules, theascarosides, which serve essential functions in regulating nematode development and behavior. Here we show that nematophagous fungi, naturalpredators of soil-dwelling nematodes, can detect and respond to ascarosides. Nematophagous fungi use specialized trapping devices to catch andconsume nematodes, and previous studies demonstrated that most fungal species do not produce traps constitutively but rather initiate trap-formation inresponse to their prey. We found that ascarosides, which are constitutively secreted by many species of soil-dwelling nematodes, represent a conservedmolecular pattern used by nematophagous fungi to detect prey and trigger trap formation. Ascaroside-induced morphogenesis is conserved in severalclosely related species of nematophagous fungi and occurs only under nutrient-deprived condition. Our results demonstrate that microbial predatorseavesdrop on chemical communication among their metazoan prey to regulate morphogenesis, providing a striking example of predator-prey coevolution.We anticipate that these findings will have broader implications for understanding other inter-kingdom interactions involving nematodes, whichare found in almost any ecological niche on Earth.A morphogenesis regulator controls cryptococcal neurotropism. Xiaorong Lin 1 , Bing Zhai 1 , Karen Wozniak 2 , Srijana Upadhyay 1 , Linqi Wang 1 , ShupingZhang 3 , Floyd Wormley 2 . 1) Biology, Texas A&M University, TAMU-3258, TX; 2) Biology, the University of Texas at San Antonio, San Antonio, Texas, USA; 3)Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.Cryptococcus neoformans is the major causative agent of cryptococcal meningitis, a disease that is responsible for more than 600,000 deaths each year.This ubiquitous environmental pathogen enters host lungs through inhalation and typically establishes asymptomatic latent infections. However,extrapulmonary dissemination often occurs in individuals with weakened immunity and Cryptococcus has a predilection to infect the brain. Braininfections are fatal and formidable to treat due to the poor penetration of most antifungals to the brain. Unfortunately, little is known about cryptococcalfactors that control its neurotropism. Here we report that a morphogenesis regulator Znf2 controls the tissue tropism of cryptococcal infection. Inparticular, activation of Znf2 abolishes Cryptococcus extrapulmonary dissemination and consequently leads to the absence of fatal brain infections in theinhalation infection model. Although Znf2 overexpression strains are avirulent in this animal model, these strains are capable of proliferating in the animallungs during the early stages of infections. Histological examinations and cytokine profiling revealed that the Znf2 overexpression strain causes enhancedmonocyte infiltration in the animal lungs. Consistently, the Znf2 overexpression strain stimulates pro-inflammatory host responses while suppressesdeleterious Th2 host responses during early stage of infection in the pulmonary infection model. Such protective host defense responses might haveprevented the extrapulmonary dissemination of Cryptococcus. In the intravenous infection model where the lung infection was bypassed and there wasuniform hematogenous dissemination, the Znf2 overexpression strain showed a specific defect in the brain infection. Taken together, our data indicatethat Znf2 helps polarize the host immunity towards protection and that it mediates cryptococcal tissue tropism during infection.Sit and wait: Special features of Aspergillus terreus in macrophage interactions and virulence. M. Brock 1 , I.D. Jacobsen 2 . 1) MicrobialBiochemistry/Physiology, Friedrich Schiller University and Hans Knoell Institute, Jena, Germany; 2) Molecular Pathogenicity Mechanisms, Hans KnoellInstitute Jena, Germany.While Aspergillus fumigatus is known as the main cause of invasive pulmonary aspergillosis in immunocompromised patients, Aspergillus terreus is anemerging pathogen prevalent in some local hot spots. When tested in embryonated egg or murine infection models A. terreus required substantiallyhigher infectious doses compared to A. fumigatus to cause high mortality rates. Furthermore, when A. fumigatus and A. terreus infections were followedby in vivo imaging using bioluminescent reporter strains, germination and tissue invasion of A. terreus was significantly delayed. To elucidate differences inmore detail, the interaction of A. terreus and A. fumigatus with macrophages was compared. A. terreus was phagocytosed significantly faster, whichappears mainly due to higher exposure of galactomannan and glucans on the surface of conidia. Additionally, although phagocytosis of both speciesresulted in phagolysosome maturation, A. fumigatus efficiently inhibited acidification, which was not the case for A. terreus. However, within this acidicenvironment of phagolysosomes A. terreus showed long-term persistence without significant inactivation of conidia. Further analyses revealed thatinefficient blocking of acidification by A. terreus was due to differences in the spore colour pigment of both species. Recombinant production of anaphthopyrone synthase from Aspergillus nidulans enabled A. terreus to inhibit the acidification to a similar extent as observed for A. fumigatus. Thisalteration of the phagolysosomal environment resulted in an increased escape from macrophages and was accompanied by increased virulence in amurine infection model. We speculate that the long-term persistence of A. terreus wild-type strains in acidified phagolysosomes might be responsible forhigh dissemination rates observed in infected human patients, because A. terreus might hitchhike inside immune effector cells to reach secondary sites ofinfection.56