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A Novel Treatment for Candida glabrata Infection

CSEF · 2016 Microbiology (General) Honorable_mention Award

Elan E. Filler · Palos Verdes High School, Palos Verdes Estates, Los Angeles County

Overview

Objectives/Goals Candida glabrata is a fungus that causes life threatening infection in humans. Recently, some strains have become resistant to current antifungal drugs such as caspofungin, and new drugs are urgently needed. Last year, I discovered that the transcriptional regulator Ada2 is required for C. glabrata to resist antimicrobial peptides and caspofungin, and is necessary for virulence in Galleria mellonella (wax moth) larvae. My hypothesis is that a compound that inhibits Ada2 can potentially be used to treat C. glabrata infection. My objective was to discover a new drug to treat C. glabrata infection. Methods/Materials Computer-assisted modelling, docking, and screening were used to identify potential Ada2 inhibitors. Ten of these compounds were selected based on structural diversity and availability and were purchased from a commercial source. To test for toxicity, each compound was injected into G. mellonella, and survival was monitored over a seven day period. Each non-toxic compound was tested for its capacity to protect G. mellonella from lethal C. glabrata infection using survival as the endpoint. Results Computer modelling generated a list of 400 potential Ada2 inhibitors. Of the 10 compounds that were selected and tested for toxicity in G. mellonella, only three were found to be non-toxic. Of these three, the compound 6-methyl-2-oxo-N-(2-pyridylmethyl)-1H-pyridine-3-carboxamide significantly improved survival of infected G. mellonella in two separate experiments (p=0.011 as compared to control by the log-rank test). Conclusions/Discussion I discovered that the compound, 6-methyl-2-oxo-N-(2-pyridylmethyl)-1H-pyridine-3-carboxamide, is a promising antifungal drug because it is nontoxic and prolongs survival in the G. mellonella model of disseminated C. glabrata infection.

Summary statement

I discovered a new compound to treat serious infections caused by the fungus Candida glabrata.

Help received

Dr. John E. Edwards, Jr. at Los Biomedical Research Institute was my mentor and provided me with guidance and laboratory space. However, I performed all the research independently.

Awards (1)

  • Honorable Mention

Competition history

  • CSEF 2016 Microbiology (General) · Entry S1507

Resources

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