There has been a dramatic rise in the number of severe fungal infections due to a constant rise 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. One promising approach is to combine current antifungal treatments with agents that enhance the host immune system's ability to eliminate the microbe. Such an approach requires a detailed understanding of the complex interaction between host and pathogen. Infections due to Candida, Aspergillus, and Mucorales are the most common fungal infections that are associated with poor outcome. Together, these three phylogenetically and biologically distinct fungi are responsible for approximately 90% of the invasive fungal infections that occurred in North America between 2004 and 2008. Here we will combine dual-species RNA-seq, comparative genome analysis, well established animal models and fungal genetics to systematically and comprehensively analyze the host-pathogen interactions of these diverse fungal pathogens. 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.

Public Health Relevance

The goal of the proposed work is to identify novel therapeutic targets to combat fungal disease by characterizing the complex interaction between the host and fungal pathogens during the course of infection. We will accomplish this be examining how 3 diverse fungi and the host change their gene expression in response one another. This information will increase our understanding of how fungi cause disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
United States
Zip Code
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:
Hazen, Tracy H; Mettus, Roberta; McElheny, Christi L et al. (2018) Diversity among blaKPC-containing plasmids in Escherichia coli and other bacterial species isolated from the same patients. Sci Rep 8:10291
Chung, Matthew; Teigen, Laura; Liu, Hong et al. (2018) Targeted enrichment outperforms other enrichment techniques and enables more multi-species RNA-Seq analyses. Sci Rep 8:13377
Watkins, Tonya N; Gebremariam, Teclegiorgis; Swidergall, Marc et al. (2018) Inhibition of EGFR Signaling Protects from Mucormycosis. MBio 9:
Andrianaki, Angeliki M; Kyrmizi, Irene; Thanopoulou, Kalliopi et al. (2018) Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species. Nat Commun 9:3333
Hazen, Tracy H; Mettus, Roberta T; McElheny, Christi L et al. (2018) Draft Genome Sequences of blaKPC-Containing Enterobacter aerogenes, Citrobacter freundii, and Citrobacter koseri Strains. Genome Announc 6:
Broxton, Chynna N; He, Bixi; Bruno, Vincent M et al. (2018) A role for Candida albicans superoxide dismutase enzymes in glucose signaling. Biochem Biophys Res Commun 495:814-820
Higginson, Ellen E; Ramachandran, Girish; Hazen, Tracy H et al. (2018) Improving Our Understanding of Salmonella enterica Serovar Paratyphi B through the Engineering and Testing of a Live Attenuated Vaccine Strain. mSphere 3:
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:

Showing the most recent 10 out of 55 publications