wild-type drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of candida albicans野生型果蝇作为模式分析氮源主机依赖白色念珠菌的毒力.pdfVIP

Wild-Type Drosophila melanogaster as a Model Host to Analyze Nitrogen Source Dependent Virulence of Candida albicans 1 2¤a 2 ˚ 1¤b 2 Monica M. Davis , Francisco J. Alvarez , Kicki Ryman , Asa A. Holm , Per O. Ljungdahl *, Ylva ¨ 1* Engstrom 1 Department of Molecular Biology and Functional Genomics, Stockholm University, Stockholm, Sweden, 2 Wenner-Gren Institute, Stockholm University, Stockholm, Sweden Abstract The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1D efg1D and csh3D fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS- sensor (Ssy1, Ptr3, and Ssy5) activates two transcription factors (Stp1 and Stp2) to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively). Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2