This research project investigates the interactions between colonizing Candida albicans cells and the GI tract environment. GI colonization with C. albicans is common for humans and generally does not have adverse effects on human health. However, if a patient becomes immunocompromised, colonizing C. albicans cells can escape the GI tract, reach the blood stream and cause disseminated disease. GI colonization is therefore significant because disease-causing fungal cells arise from the populations that colonize the host as harmless commensals. In addition, preliminary results show that, under certain conditions, colonization with C. albicans increases the resistance of the host to lethal challenge with an enteric bacterial pathogen. The long term goals of the proposed research are to understand the mechanisms by which C. albicans alters the GI tract environment and affects host resistance to challenge. The focus of Specific Aim 1 is to identify C. albicans activities that detoxify antimicrobial compounds.
In Specific Aim 2, the goal is to understand how C. albicans alters the metabolite milieu of the GI tract. The studies proposed in Specific Aim 3 will analyze the effects of C. albicans colonization on the composition of the gut microbiota. These studies will increase the understanding of the interplay between C. albicans and the mammalian GI tract environment. Deeper understanding will enable development of novel interventions that harness the beneficial effects of C. albicans in the GI tract.

Public Health Relevance

Although Candida albicans is an important pathogen of hospitalized or otherwise immunocompromised patients, recent results show that when C. albicans colonizes the murine gut, the host is more resistant to infection by a bacterial pathogen. This research seeks to understand the C. albicans activities that are important to allow the organism to persist in the GI tract and to protect the host from infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI118898-04
Application #
9765139
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Love, Dona
Project Start
2016-09-23
Project End
2021-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Tufts University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C et al. (2018) A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage. Anaerobe 50:85-92
Markey, Laura; Shaban, Lamyaa; Green, Erin R et al. (2018) Pre-colonization with the commensal fungus Candida albicans reduces murine susceptibility to Clostridium difficile infection. Gut Microbes 9:497-509
Herwald, Sanna E; Zucchi, Paola C; Tan, Shumin et al. (2017) The two transmembrane regions of Candida albicans Dfi1 contribute to its biogenesis. Biochem Biophys Res Commun 488:153-158