There has been a dramatic rise in the number of severe fungal infections due to a constant increase in the number of individuals who are immunocompromised. Strong similarities in the basic eukaryotic metabolic pathways between fungi and mammalian cells have hindered the development of antifungal agents because many compounds that are effective at inhibiting fungal growth are also toxic to host cells. It is becoming clear that novel antifungal agents alone are unlikely to significantly reduce the mortality rate of fungal infections without the aid of new therapeutic approaches. Promising alternative approaches include combining current antifungal treatments with agents that enhance the host immune system's ability to eliminate the microbe or disrupt an interspecies molecular interaction that governs invasion. These approaches require a detailed understanding of the complex interaction between host and pathogen. This proposal will focus on three emerging fungal pathogens - Scedosporium spp, Candida auris and Mucorales fungi. Infections with these three phylogenetically distinct pathogens frequently fail to respond to currently available antifungal therapy and are therefore associated with extremely high mortality rates. Here we will combine dual-species RNA-seq, comparative genome analysis, established animal models and fungal genetics to systematically and comprehensively analyze the host-pathogen interactions for each class. Analyzing all three different types of fungi using the same approach will enable us to define commonalities as well as key differences among the organisms and the responses they elicit in the host. The proposed studies will provide a wealth of information regarding gene function and regulation in both the fungus and the host and will likely lead to the identification of novel therapeutic targets to treat this increasingly serious cause of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI110820-07
Application #
9901444
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Richter, Taylor K S; Hazen, Tracy H; Lam, Diana et al. (2018) Temporal Variability of Escherichia coli Diversity in the Gastrointestinal Tracts of Tanzanian Children with and without Exposure to Antibiotics. mSphere 3:
Baldin, Clara; Soliman, Sameh S M; Jeon, Heewon H et al. (2018) PCR-Based Approach Targeting Mucorales-Specific Gene Family for Diagnosis of Mucormycosis. J Clin Microbiol 56:
Liu, Hong; Xu, Wenjie; Solis, Norma V et al. (2018) Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity. Virulence 9:1062-1073
Richter, Taylor K S; Michalski, Jane M; Zanetti, Luke et al. (2018) Responses of the Human Gut Escherichia coli Population to Pathogen and Antibiotic Disturbances. mSystems 3:
Ouattara, Amed; Tran, Tuan M; Doumbo, Safiatou et al. (2018) Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte-Binding Protein Homologue-5 in Kalifabougou, Mali. Am J Trop Med Hyg 99:43-50
Mendes, António M; Machado, Marta; Gonçalves-Rosa, Nataniel et al. (2018) A Plasmodium berghei sporozoite-based vaccination platform against human malaria. NPJ Vaccines 3:33
Chung, Matthew; Teigen, Laura; Libro, Silvia et al. (2018) Multispecies Transcriptomics Data Set of Brugia malayi, Its Wolbachia Endosymbiont wBm, and Aedes aegypti across the B. malayi Life Cycle. Microbiol Resour Announc 7:
Watkins, Tonya N; Liu, Hong; Chung, Matthew et al. (2018) Comparative transcriptomics of Aspergillus fumigatus strains upon exposure to human airway epithelial cells. Microb Genom :
Robertson, Colin D; Hazen, Tracy H; Kaper, James B et al. (2018) Phosphotyrosine-Mediated Regulation of Enterohemorrhagic Escherichia coli Virulence. MBio 9:
Ndungo, Esther; Randall, Arlo; Hazen, Tracy H et al. (2018) A Novel Shigella Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge. mSphere 3:

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